tag:blogger.com,1999:blog-18878668197302064892024-03-21T15:33:14.083-06:00Fantastic Voyage: A journey through my DNA and Personal GenomicsGrant M. Woodhttp://www.blogger.com/profile/18185402177712853914noreply@blogger.comBlogger15125tag:blogger.com,1999:blog-1887866819730206489.post-33543100921194257072010-04-26T19:43:00.013-06:002010-04-27T09:59:33.478-06:00Clinical Genetics Institute celebrates its 5th birthday with an open house on May 3rd<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg_469ykM_xAw2HHFPI6a7bzDWZkC-sETvWb6zNEXMu_IyKFnlKDzcSX-zcvaaznr-aFqYB38P2jZXdAhgrSuYrkez4yVrDJgdLs_9-yYO11oF1dCcNV8h7WnMMPds2iMS6iUFGlRkAnILF/s1600-h/MarcSWilliams-thumb.jpg"><img id="BLOGGER_PHOTO_ID_5341272521423463202" style="FLOAT: left; MARGIN: 0px 10px 10px 0px; WIDTH: 78px; CURSOR: hand; HEIGHT: 78px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg_469ykM_xAw2HHFPI6a7bzDWZkC-sETvWb6zNEXMu_IyKFnlKDzcSX-zcvaaznr-aFqYB38P2jZXdAhgrSuYrkez4yVrDJgdLs_9-yYO11oF1dCcNV8h7WnMMPds2iMS6iUFGlRkAnILF/s320/MarcSWilliams-thumb.jpg" border="0" /></a><br /><br /><strong>Perspective from a medical geneticist</strong><br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhyAclh_RrK_-O3UFXeOdNNapzwCv9EgwDWaiyfHNXEfk3ckWFYPgswnPVZprYUIM_GhgosVkiCgnMtF7a0IfPy5K5SAexqoAhi7tUxbUZ6j04Bc2yAvTnaz-wmB3yuJUSogaoUeo6i4kZF/s1600/Fifth+Birthday+cropped.jpg"><img style="display:block; margin:0px auto 10px; text-align:center;cursor:pointer; cursor:hand;width: 400px; height: 347px;" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhyAclh_RrK_-O3UFXeOdNNapzwCv9EgwDWaiyfHNXEfk3ckWFYPgswnPVZprYUIM_GhgosVkiCgnMtF7a0IfPy5K5SAexqoAhi7tUxbUZ6j04Bc2yAvTnaz-wmB3yuJUSogaoUeo6i4kZF/s400/Fifth+Birthday+cropped.jpg" border="0" alt=""id="BLOGGER_PHOTO_ID_5464840792948374146" /></a><br />Hard to believe it’s been over 5 years since we opened our doors. I’m not one to rest on accomplishments or spend a lot of time looking backwards, but I think our early childhood has had some significant milestones—not to mention some teething pains!! I would highlight the inclusion of links to genetic information within our electronic health record resources; developing techniques for rapid technology assessment of emerging genetic tests which lead to the formation of the Genetic Testing Practice Council; initiation of Cancer Genetic Services that now serves LDS, IMED, McKay-Dee and Logan Regional Hospitals; deployment of a tumor based screening program for Lynch syndrome, electronic communication of genetic test results and a lot of work on the use of family history.<br /><br /><strong>Communication</strong><br /><br />One of our goals for 2010 was to improve communication between the CGI and the outside world—and not just the Intermountain Healthcare world, but the entire world as it were. To this end we’ve been able to move our website outside the Intermountain firewall. If you’d like to see it go <a href="http://intermountainhealthcare.org/genetics/">here</a>. We’ve also started to use social media sites including Facebook and this blog. Anita Pascoe, our newest team member, has been doing some interesting work on web traffic. We hope to have more for you later in the year, potentially including some more posts on Grant’s genome. All of the team members have had the opportunity to present our work at a number of national and international meetings. Visit our <a href="http://intermountainhealthcare.org/genetics/">website</a> for more details about our various projects.<br /><br /><strong>People</strong><br /><br />Amazingly enough we’ve had almost no turnover of our team. Cami Bills who was the program administrative assistant for three years left for a position that was a bit closer to her home but she remains a BFF of the CGI. Anita Pascoe joined the team 2 years ago and has been working hard on aspects of team building and communication. She has also become an invaluable part of other Intermountain Healthcare communication teams particular for research. Janet Williams now works as the Oncology Genetic Counselor and is running that program. She stays engaged with our team in development of our family history tools. We’ve also developed a close working relationship with members of the Homer Warner Center for Informatics Research, particularly Nathan Hulse and Peter Haug. This has been a fun and fruitful collaboration.<br /><br /><strong>The Future</strong><br /><br />“Prediction is difficult, especially when it involves the future.” (That quote has been famously misattributed to Yogi Berra, George W. Bush, Dan Quayle and others. It was actually Niels Bohr the Nobel Prize-winning nuclear physicist.) That said, there are a number of exciting things for the CGI on the near horizon. First among these is the launch of our patient-entered family history tool which will go live on our patient portal in July. We are currently testing the tool’s user interface to work out some bugs, but the biggest opportunity to learn will be when the tool is exposed to the Intermountain patient population. We will be studying how patient’s interact with the tool (something that has not been done to a significant degree with other family history tools); what information is entered; how patients communicate information with their providers; and does it change health behavior. We are also going to be directly linking patient information about health conditions using infobuttons so users can download information about health conditions in themselves and their families.<br /><br />We are also looking to establish electronic communication of genetic laboratory results from our largest referral laboratory. This could dramatically improve our ability to link information for the clinicians to the report which we think would help with interpretation. The biggest project will be to work with the team that is developing the new Clinical Information System to make sure that it has the capability of handling genetic and family history information. Lots of work to do—but that is the fun of genetics.<br /><br /><strong>Invitation</strong><br /><br />We hope that those of you in the Salt Lake area are able to stop in for our open house on May 3rd. See the flyer for details. Be sure to wear your designer genes!!<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiZ8pOPSbqOv-BlPeMKs3y3486WhRfYxS-o03H-He_vQ22MGjQWo2EgMU_VpnLMz6IwZqgLTHD64uLed4c6cuX5yTCIS7F0e1Lecsus5HfuRYBMCrP-hLo8gzTRWUzdUCTcAmd1jdT6ju3y/s1600/CGI+Open+House.JPG"><img style="display:block; margin:0px auto 10px; text-align:center;cursor:pointer; cursor:hand;width: 309px; height: 400px;" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiZ8pOPSbqOv-BlPeMKs3y3486WhRfYxS-o03H-He_vQ22MGjQWo2EgMU_VpnLMz6IwZqgLTHD64uLed4c6cuX5yTCIS7F0e1Lecsus5HfuRYBMCrP-hLo8gzTRWUzdUCTcAmd1jdT6ju3y/s400/CGI+Open+House.JPG" border="0" alt=""id="BLOGGER_PHOTO_ID_5464843783616012146" /></a><em>Click on image to enlarge</em>Grant M. Woodhttp://www.blogger.com/profile/18185402177712853914noreply@blogger.com12tag:blogger.com,1999:blog-1887866819730206489.post-11164703849961594742009-12-27T23:45:00.004-07:002009-12-28T00:21:16.832-07:00Got Gout?After returning to work from the Thanksgiving holiday, I was asked by Marc and Janet if my 23andme report contained anything about <a href="http://en.wikipedia.org/wiki/Gout">Gout</a>. Janet said Gout was a topic of conversation while visiting with her family. Sure enough, I found Gout listed in my elevated-risk section of the Research Report. (Remember, the information in the research report section “has not yet gained enough scientific consensus to be included in [23andme’s] clinical report.”<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhdC0NrvBXz5aBacivLGf5KinxtA1GAi7GhrteGSKTxt7AVAzvGYN6Fx11oRVRiUCG04wFmnzt91eMDDciXHFXV5kmCoBnsWHmG-NCLh9Aw_rXdyksWDztHirOM7geEDBrAn7jUx7CblRes/s1600-h/23andme+Research+Report+Elevated+Risk.jpg"><img id="BLOGGER_PHOTO_ID_5415933714672632754" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 328px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhdC0NrvBXz5aBacivLGf5KinxtA1GAi7GhrteGSKTxt7AVAzvGYN6Fx11oRVRiUCG04wFmnzt91eMDDciXHFXV5kmCoBnsWHmG-NCLh9Aw_rXdyksWDztHirOM7geEDBrAn7jUx7CblRes/s800/23andme+Research+Report+Elevated+Risk.jpg" border="0" /></a><br /><span style="font-size:85%;"><em>Click to enlarge image</em></span><br /><br />Two stars means the confidence level in the research is currently low. The website instructs me that “the condition (Gout) is caused by the accumulation of crystallized uric acid in the internal organs and joints – particularly in the big toe – which causes painful arthritic inflammation.”<br /><br />23andMe looks at 3 SNPs in the SLC2A9 gene to determine my risk for developing Gout. If you have a certain mutation in these three SNPs, your odds increase by 1.3, 1.3, and 1.4 times (for each SNP). I have one mutation out of the three possible, so I only have “slightly higher odds”.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgZ5AfYkWT74AJNhdSLuSLrZMGFXAV8h052v5Mv2mnXRVEB8aYh3Jo9OpjiBc80XRasq9SpvKx0tPZvrymIogszo8yJAHOIUlfQgBtpqTb-N8g3BatNw4VDXygYSzI4DqEtAj5F1c7o4Por/s1600-h/23andme+Gout+one+SNP+higher+odds.jpg"><img id="BLOGGER_PHOTO_ID_5415933908435525378" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 249px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgZ5AfYkWT74AJNhdSLuSLrZMGFXAV8h052v5Mv2mnXRVEB8aYh3Jo9OpjiBc80XRasq9SpvKx0tPZvrymIogszo8yJAHOIUlfQgBtpqTb-N8g3BatNw4VDXygYSzI4DqEtAj5F1c7o4Por/s800/23andme+Gout+one+SNP+higher+odds.jpg" border="0" /></a><br /><span style="font-size:85%;"><em>Click to enlarge image</em></span><br /><br />The most interesting bit of knowledge I learned is the dietary factors that increase risk for Gout – high fat, alcohol and protein consumption are common for those who develop the disease. One fellow 23andMe customer shared that he was eating meat and drinking beer everyday for a year for his Adkins diet. He didn’t say if he lost weight, but did say his Gout was painful - and his diet has since changed. Another person commented that a <a href="http://www.ncbi.nlm.nih.gov/pubmed/15934094">study</a> found a supplement of 500mg of vitamin C per day over 2 months reduced uric acid levels in the blood of 184 men.<br /><br /><br /><img id="BLOGGER_PHOTO_ID_5415934595192711378" style="DISPLAY: block; MARGIN: 0px auto 10px; WIDTH: 320px; CURSOR: hand; HEIGHT: 235px; TEXT-ALIGN: center" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhUB4zKFDMZLbqr3EUKdxA4DWtrzbG_I33OH0PjO4XD97sEu2XTed6k7uGtG7Q4TZEY8JMkWYofUXKZNVlOemi-xuu1TClLIRNk8Nu99wRiWHvInjMfbDehRvtrzauOcjkuFfeyi3nnSSbE/s320/gout+demon.bmp" border="0" /><br /><p align="center"><span style="font-size:78%;"><em>The Gout. James Gillray, 1799. From the Philadelphia Museum of Art.</em></span></p><p><strong>See You Next Year</strong></p><p>Taking a two-week vacation for the holidays took a toll on the timeliness of this post. So let me wish everybody a belated Seasons Greetings, and an extra wish for that Happy New Year.</p><p><br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg5thXQ6wHs_OATtsXM_Xhyphenhyphenit8FJeyt38FXsDHz_the6iWNOU4VqEuprIBIVS03SvFzUtqDZzFtZ1Se7xldRETYFEFgta3NbuhlcqBun3RqfMA6OIUVdzcD_B6HS1i8px5tCLhV3qHv3344/s1600-h/Janet+A+001-1.jpg"><img id="BLOGGER_PHOTO_ID_5363017094122700610" style="FLOAT: left; MARGIN: 0px 10px 10px 0px; WIDTH: 89px; CURSOR: hand; HEIGHT: 100px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg5thXQ6wHs_OATtsXM_Xhyphenhyphenit8FJeyt38FXsDHz_the6iWNOU4VqEuprIBIVS03SvFzUtqDZzFtZ1Se7xldRETYFEFgta3NbuhlcqBun3RqfMA6OIUVdzcD_B6HS1i8px5tCLhV3qHv3344/s200/Janet+A+001-1.jpg" border="0" /></a><br /><strong><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjUC1pRX2YY0sOHY4eYu7Qh-rsRksUQ71kXpKIgMb666WCyj7GSRaygHe-ip7xwDcGTwL-SxD73CbdPo1XEwxh_qvfu1BCmgKEPhskcd00biSmwGvjELsU2vzvYvKREPP2hPF_OeSe8GEce/s1600-h/jwilliams.jpg"></a></strong><br /><strong>Perspective from a Certified Genetic Counselor</strong><br /><br /><br /><br /><br /><strong>Gout and the Holidays</strong><br /><br />It is difficult to find time to write a blog submission in this season of merriment. Saturday evening is the church wine and cheese party; Sunday evening is the book club potluck; Monday is team breakfast, followed by small group lunch potluck, followed by a departmental dinner that evening. This is just the next three days! With the holiday season comes all the wonderful food. So you might think that we decided to talk about risk association and gout because of the known relationship between wonderful food and gout. It is a reasonable assumption. However, the truth is that while I was home over Thanksgiving I learned that more than one of my family members is reported to have had gout—including my mother! I made the mistake of musing aloud with Marc, “I wonder if the 23andme report addresses risk for gout?” upon which Marc, ever resourceful and ready to delegate [dump!], replied, “Yours, December 14th”.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhYVD4PY4BTpyQkXEwXV_j1rKhoTEHslFLi5BB1DrFyYBbiM5zLqke4uGMX4BHqKRH-aSQkwAqM7QjM9-cbRhM5lKT3vXYx5BMHZoDvvAYwgdW9BsXWV97qP9vm5HqZ536jEZA5f3oEBaR3/s1600-h/gout+a+royal+pain.jpg"><img id="BLOGGER_PHOTO_ID_5415934891661972754" style="FLOAT: right; MARGIN: 0px 0px 10px 10px; WIDTH: 320px; CURSOR: hand; HEIGHT: 280px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhYVD4PY4BTpyQkXEwXV_j1rKhoTEHslFLi5BB1DrFyYBbiM5zLqke4uGMX4BHqKRH-aSQkwAqM7QjM9-cbRhM5lKT3vXYx5BMHZoDvvAYwgdW9BsXWV97qP9vm5HqZ536jEZA5f3oEBaR3/s320/gout+a+royal+pain.jpg" border="0" /></a><br />Gout is famous for its appearance in royal families throughout many centuries. It is more recently that the general diet for people living in Western societies has “improved” to the point that gout is more common. Gout is a great example of the complexity of common adult onset disease. It is quite significantly impacted by familial factors. But genetic factors are NOT the whole picture. It is influenced by gender and age (more men develop gout than women and older age increases appearance especially in women post-menopause), obesity and metabolic syndrome increase the chance that gout may develop, and those with hypertension and cardiovascular disease more often are diagnosed with gout. Finally, specific dietary choices and life events may lead to gout symptoms. The challenge has been to identify the specific contributors that lead to gout in the hope that effective medications can be given to prevent the painful episodes and joint damage that result from uric acid deposition.</p><br /><p><strong>Elegantly Balanced</strong><br /><br />The work to elucidate the mechanisms, metabolism and mystery of gout has led to new understanding of pathways and inter-relatedness of human (mammal) systems biology. We are so very complex and elegantly balanced, physiologically speaking! The development of gout is, for the most part, dependent on the levels of uric acid floating around in the blood stream. People with gout either produce too much uric acid, or more commonly, their bodies have a problem in removing it. Uric acid is one of the inescapable products of the breakdown of food and processing of cells. The kidneys are responsible for the majority of the management of uric acid. This is a version of gout for dummies—please use your healthcare provider for a real discussion of gout!<br /><br />Grant’s 23andme report indicates that he is at elevated risk for gout. The report lists identified markers in the SLC2A9 urate transporter which is formally known as the solute carrier family 2 member 9 and its function is to move uric acid and glucose/fructose. Common variants in SLC2A9 are associated with increased levels of uric acid and gout. Of the three markers assessed in his report, he had two which conveyed typical risk and one (rs737267 “GG”) which conveyed 1.3 times the odds of gout. Grant’s result is given two stars (out of 4?) in research confidence. This may be because so many other SNPs appear to affect uric acid levels. In a recent meta-analysis published in Public Library of Science Genetics, researchers evaluated 28,141 participants of European descent and identified 954 SNPs in 9 locations that had genome-wide significance with impact on serum uric acid levels. Certain SNPs lead to more pronounced effect in uric acid levels in women, while other SNPs elevate uric acid more strongly in men. The writers go on to suggest that it is the interplay between the SNPs, other proteins in the cellular environment and the uric acid levels in the blood that will contribute to whether one develops gout.</p><br /><p><strong>Gout and the Family</strong><br /><br />What about me and gout in my family? First of all, I do have two first degree relatives known to have gout. I recall that a brother had one experience with a really painful big toe that was labeled gout. I knew that my maternal uncle had to give up milking up cows because of arthritis in his knees—reported as osteoarthritis due to repeatedly kneeling to hook-up milking machines (pretty plausible). I knew that my grandfather had arthritis so bad that he sometimes had to crawl to the barn (no milking machines). I knew that my mother had a serious flare of non-rheumatoid arthritis in her feet, so bad that she could not keep the sheet resting on her toes. But I did not know that it was labeled gout and I haven’t even mentioned the family history of kidney stones. The brother above has had kidney stones that tested positive for uric acid. Now comes the “do I have…”, the episodes of curiously sharp pain in my big toe joint??? Was it just the choice of shoes???? </p>Grant M. Woodhttp://www.blogger.com/profile/18185402177712853914noreply@blogger.com43tag:blogger.com,1999:blog-1887866819730206489.post-7877161828545081092009-11-23T17:00:00.005-07:002009-11-25T12:05:49.076-07:00Pass the Turkey, Pie, Football, … and Family Health HistoryBecause Thanksgiving Day is also Family Health History Day, we’ve decided to suspend showing results from my <a href="https://www.23andme.com/">23andMe</a> report for this post and review Family Health History activities <a href="http://intermountainhealthcare.org/services/genetics/Pages/home.aspx">Intermountain Healthcare’s Clinical Genetics Institute</a> is leading. We consider clinically-used family history to be the cheapest and most effective genetic test today.<br /><br /><strong>Prologue</strong><br /><br />Former Secretary of HHS <a href="http://en.wikipedia.org/wiki/Mike_Leavitt">Mike Leavitt</a> tells a story of when he was governor of the State of Utah. A research program to find the genetic cause for disease needed to recruit large families for the study. Gov. Leavitt met a grandfather who said "I think there's something to this genetics thing. I'm 71 years old, and when I turned 70, I was diagnosed as having <a href="http://en.wikipedia.org/wiki/Macular_degeneration">macular degeneration</a>. When my father was 70 years old, he got macular degeneration. In fact when his father turned 70 years old, he got macular degeneration."<br /><br />He said, "If there's something I can do and my family can do to keep my grandson or my great grandson from having that moment when he turns 70 years old, I want to do it, and I'm in."<br /><br />We hear many stories just like this. The older generation wants to know how they can help the younger generation prevent the healthcare problems that run in their family.<br /><br />This grandfather’s family, in conjunction with other families, led to the discovery of the association of changes in the <a href="http://ghr.nlm.nih.gov/gene=cfh">Complement factor H</a> (or CFH) gene with this form of macular degeneration. Not only was the gene identified, but it led to the understanding that some forms of macular degeneration are inflammatory diseases, and anti-inflammatory treatments are now available to slow or halt progression of the disease.<br /><br />My 23andMe report includes age-related macular degeneration as one of the 11 diseases in the clinical reports category. It tells me that when I’m 70 years old, my absolute risk will be 1.4%, compared with 2.4% in the general population.<br /><br /><strong>Traveling to Grandmothers House - Where Are We Today?</strong><br /><br />Obviously, we want to tell patients to do a family health history and we want them to share it with their family members - and with their healthcare providers. But where are we today with this process? Are you tired of filling out the same family history form every time you visit a new doctor? Are doctors using the information effectively? Do they have the right electronic tools that can guide them to understand your risk, or for further evaluation, order the appropriate genetic test? Sadly, the answers to these questions are most likely not very positive.<br /><br /><strong>The Feast Begins - Family History in the Electronic Health Record</strong><br /><br />Within Intermountain Healthcare, there are multiple forms (both computer and paper-based) collecting family health history information from many entry points into the healthcare system. The vast majority of family history is captured by the doctor in the medical computer – but in a text-based clinical note – which means the computer can’t understand it and do anything with it.<br /><br />Except for those used by genetic counselors, most family history collection tools used today do not allow for the building of pedigrees, nor do they ask for other critical information, like the age of onset of a relative’s disease. Our current tools do not gather the data required to create a disease risk assessment for the patient. The Clinical Genetics Institute at Intermountain is beginning to rewrite these family history programs in the EHR.<br /><br /><strong>The Main Course - What We Want to Create</strong><br /><br />As a group focusing on family health history, we’ve had a lot of time to ponder what we want to see in future electronic tools - tools that capture and analyze family health history information to advance clinical care. We would like to start with a general tool that collects information about the common diseases your primary care physician would be interested in. The program would then expand into more targeted areas to ask questions that a specialty physician would want to know about a specific disease or condition for which the patient is seeking treatment.<br /><br />A key goal for this project is to provide useful risk assessment reports for both the patient and the doctor. First, the report should contain information for the patient to act on - information that will encourage behavior change, or to seek out appropriate screening tests, or possibly further genetic testing, and hopefully, sharing the results with other family members.<br /><br />Secondly, the report should provide information for the doctor to review and validate for accuracy since the information will be stored in the EHR. When the data is stored in a structured and coded format, the computer can offer the doctor clinical decision support messages - which becomes powerful when clinical and genetic/genomic data are included in the decision algorithms. Having family health history records can guide the physician in ordering the most appropriate genetic test when testing is indicated.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjqc1Ihir8KzzxbQNVWIkhweeNMonua0d3yjLXtYiy9g4xSbuEkJSBy0J3tWe8ZOg6EF4gEiA3metP6XqNxuFr2vYlaEbvE29pMWBTyXMhRnUC1lTFcVxz3En2_JkdX9dk19Kg85xfCVTVz/s1600/CME+graphic+family+history.jpg"><img id="BLOGGER_PHOTO_ID_5407430570607545010" style="WIDTH: 400px; CURSOR: hand; HEIGHT: 280px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjqc1Ihir8KzzxbQNVWIkhweeNMonua0d3yjLXtYiy9g4xSbuEkJSBy0J3tWe8ZOg6EF4gEiA3metP6XqNxuFr2vYlaEbvE29pMWBTyXMhRnUC1lTFcVxz3En2_JkdX9dk19Kg85xfCVTVz/s400/CME+graphic+family+history.jpg" border="0" /></a><br />© Intermountain Healthcare 2009. All rights reserved.<br /><br /><strong>Pouring On the Gravy - New Tools for Patients</strong><br /><br /><a href="http://healthvault.com/">Microsoft HealthVault</a> announced a grant program called the <a href="http://www.healthvault.com/industry/whats-new/fund/rfp.html">Be Well Fund</a> in 2008. The Genetics Institute became one of 15 award recipients and began a project creating a web-based, patient-entered family health history program. When completed, the program will be hosted on Intermountain’s patient portal called ‘<a href="http://intermountainhealthcare.org/health/myhealth/Pages/home.aspx">MyHealth</a>’. The application will store the data in Intermountain’s clinical data repository, thereby making it available to healthcare providers via the electronic health record. If the user is interested in having a HealthVault account, they upload their data to that account by simply clicking a button. We hope to have this program go live in the Spring of 2010. In the spirit of the grant, we will attempt to make the code available via open source for others to implement.<br /><br /><em>A screen shot from our family history program under development</em><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiak93SWG4q4vEDJ9a6ZYS-4P0fvIlOX5XaojBigjYka4SR0tKqL7tDrH07Xv8easAufdQoSLPmgV1HnlIP7h5YghP63x9e8IGOvqV19Bm82UlAB8uZ_xyGLHCykVM_ysUKgGMS_XUE_nH7/s1600/CGI+Healthvault+main+tree+screen3.jpg"><img id="BLOGGER_PHOTO_ID_5407431591691758978" style="WIDTH: 400px; CURSOR: hand; HEIGHT: 197px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiak93SWG4q4vEDJ9a6ZYS-4P0fvIlOX5XaojBigjYka4SR0tKqL7tDrH07Xv8easAufdQoSLPmgV1HnlIP7h5YghP63x9e8IGOvqV19Bm82UlAB8uZ_xyGLHCykVM_ysUKgGMS_XUE_nH7/s400/CGI+Healthvault+main+tree+screen3.jpg" border="0" /></a><br />© Intermountain Healthcare 2009. All rights reserved.<br /><br />Intermountain's MyHealth patient portal already includes a family health history page that offers two PDFs for download on family history questions. The first booklet guides the patient on how to collect family history information, and how to ask family members for their history and that of deceased relatives. The second booklet teaches more about genetics and how it may affect familial disease. These booklets are availabe for anyone to use from the <a href="http://familyhealthhistory.org/index.php">Genetic Alliance</a>, and are fully customizable for use with any group or organization.<br /><br /><strong>Remember Your Table Manners - We Have Standards</strong><br /><br />The international healthcare data standards group <a href="http://www.hl7.org/index.cfm">HL7</a> has developed the Pedigree (Family History) model as a data transmission standard to exchange family history data between systems and applications. Besides becoming an HL7 standard, the model has become an American National Standard Institute (ANSI) standard, and is in the process of being approved by the International Standards Organization (ISO). Our patient-based family history tool, along with the tools mentioned in the following paragraph, is built around this standard. However, major healthcare software vendors have yet to implement the standard in their products, even though federal standards efforts like the Healthcare Information Technology Standards Panel (HITSP) and the Center for Certification of Healthcare Information Technology (CCHIT) will require them in the near future.<br /><br /><em>A diagram of the HL7 Pedigree (family history) model - click to enlarge</em><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjcq8GQA6j3e6BnpbjYngNAZ0KgMxMI6QsmVPE3vNoyyaaxjgduVx_jze2nenmU8Xj5KKA5_ZMjbpVoI3fWzRehHTpimk4nhYDhj8i08umqic6Cg7ljMc-J1dDOcxjsE9Eku5PH9wFJck6p/s1600/FamilyHistory-v16b.jpg"><img id="BLOGGER_PHOTO_ID_5407432334023691858" style="WIDTH: 400px; CURSOR: hand; HEIGHT: 276px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjcq8GQA6j3e6BnpbjYngNAZ0KgMxMI6QsmVPE3vNoyyaaxjgduVx_jze2nenmU8Xj5KKA5_ZMjbpVoI3fWzRehHTpimk4nhYDhj8i08umqic6Cg7ljMc-J1dDOcxjsE9Eku5PH9wFJck6p/s400/FamilyHistory-v16b.jpg" border="0" /></a><br />© Health Level Seven 2009. All rights reserved<br /><br /><strong>Here Comes the Dessert - Other Great Family History Tools Freely Available</strong><br /><br />The Office of the Surgeon General in the United States encourages people to use its web-based family health history tool while families are gathered over the Thanksgiving holiday. But did you know that the Surgeon General’s <a href="https://familyhistory.hhs.gov/fhh-web/home.action">My Family Health Portrait</a> code is also openly available? And to practice what we preach, all of the US federal healthcare computer systems, which includes the Dept. of Defense for active military, the Veterans Administration for retired military, and Indian Health Service, will be basing their family history programs on the Surgeon General’s tool, especially adhering to all of the standards upon which it was built.<br /><br />One of the most advanced clinical tools centered around family history is <a href="http://www.hughesriskapps.net/">Hughes riskApps</a>. This program identifies and manages women at high risk for hereditary breast/ovarian cancer, although they plan to expand it in the future to handle other cancers as well. The key components of the software are that it allows for patient-entered family history and other health data via a hand-held tablet. The information goes directly to the healthcare provider where several risk models are run to help determine the cancer risk of the patient. You can download the software for free from their website.<br /><br /><strong>Saving the Leftovers - Warehousing Family History Data for Research</strong><br /><br />Having great family health history data collection tools is just the beginning in reaching our goals in this area. Using the data to explore clinical research questions will open up other opportunities, which will lead to genetic/genomic - or dare I say – personalized medicine discoveries.<br /><br /><em>A diagram of a family history datamart - click to enlarge</em><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgoJE8zdLf5FMZVmHA1UGRMUkFgSrHoQPEamd-cwdZhL4vi9uBUENA3wPfr91H7OxDCTymkOXWpueBJSU8pX5HOOC4xkoY4Z5nQhyZB1eFMpGXOrRByunt35IgnrT7EvcnngROWzXK3fyrF/s1600/family+history.jpg"><img id="BLOGGER_PHOTO_ID_5407440818523944466" style="WIDTH: 400px; CURSOR: hand; HEIGHT: 239px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgoJE8zdLf5FMZVmHA1UGRMUkFgSrHoQPEamd-cwdZhL4vi9uBUENA3wPfr91H7OxDCTymkOXWpueBJSU8pX5HOOC4xkoY4Z5nQhyZB1eFMpGXOrRByunt35IgnrT7EvcnngROWzXK3fyrF/s400/family+history.jpg" border="0" /></a><br />© Intermountain Healthcare 2009. All rights reserved.<br /><br /><strong>Time to be Thankful</strong><br /><br />When your belly is full, your family is around you, and everybody is healthy, it is certainly time to be grateful. I would wish that everybody could enjoy those blessings. To add to my abundant portion, I must also mention what a wonderful opportunity it is to work in healthcare IT, and more specifically, to work in the emerging and exciting field of clinical genomics and personalized medicine. My list of things to be thankful for is much longer, but to not stop you from getting that second slice of pumpkin pie, let me just say to everyone a Happy Thanksgiving, and may your plate be filled with a healthy family history.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgZJzEL_Wjwp15d1gQ2TLtCt6fsRjz3bHjHL5kk4wE1q8JJUyNysMrxQlPMqSezaNFL-0Tde_uwRtJXmTAA9wkEFI9nHyFvTtrYOL0Zt4vBMwIxQVV3OjC_KvHU3C-aMi2zwaIrdTEN5tBy/s1600/Wood_Family_2.jpg"><img id="BLOGGER_PHOTO_ID_5407449673380538418" style="WIDTH: 400px; CURSOR: hand; HEIGHT: 248px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgZJzEL_Wjwp15d1gQ2TLtCt6fsRjz3bHjHL5kk4wE1q8JJUyNysMrxQlPMqSezaNFL-0Tde_uwRtJXmTAA9wkEFI9nHyFvTtrYOL0Zt4vBMwIxQVV3OjC_KvHU3C-aMi2zwaIrdTEN5tBy/s400/Wood_Family_2.jpg" border="0" /></a><br /><em>This picture was taken in 2008 for my parents 50th wedding anniversary. Grandma would not be pleased if I didn't point out that, since the photo was taken, two granddaughters and one more great-grandson have been born.</em>Grant M. Woodhttp://www.blogger.com/profile/18185402177712853914noreply@blogger.com15tag:blogger.com,1999:blog-1887866819730206489.post-87867531524683751592009-11-05T23:00:00.000-07:002009-11-05T23:21:50.477-07:00My Family History of Heart Disease … I ThinkWith November proclaimed to be Family History Awareness month, I thought I would write about a medical condition that runs in my family. But to what extent my relatives had this disease, or what it means for my risk, I’m not sure. If a doctor were to ask me if I have a family history of heart disease, my first response would be no. I’m not aware of any 1st, 2nd, or even 3rd degree relatives who have had heart attacks. But wait… My father did have that double bypass 12 years ago… It’s funny how I don’t think about it much. Maybe I should.<br /><br />Dad didn’t seem to be the type that was at risk. A non-smoker, non-drinker, slender, and active, he started to feel chest pain at age 63 whenever he did something physical. The pain increased gradually over time, and Dad put off seeking medical attention until it became serious. A procedure in the cardiovascular catheter lab revealed a dangerous blockage the coronary arteries. He was immediately rushed into surgery.<br /><br />It was determined that his blockage was caused by cholesterol (ding, that bell is ringing for me). His double bypass included a stent. What is interesting though is that he mostly remembers the psychotic reaction he had after the surgery (which happens to patients 10-20% of the time) because they used a heart/lung machine.<br /><br /><strong>One More Time</strong><br /><br />Nine years later he started having chest pain again, but thought it was indigestion. (What do former hospital CEOs know about medicine anyway). Sometime later he was in the hospital for a MRI that was looking for a neurological problem. In the middle of that procedure, his chest pain returned and was very severe. Knowing his history, the clinical people determined he was having a heart attack – in the hospital, thank God. His blockage had returned and a new stent was installed.<br /><br /><strong>Any Other History?</strong><br /><br />So I began asking my mother questions about any other family history of heart disease. Both of my grandfathers died (their hearts stopped) immediately following surgery that was not heart-related. They were 78 years old. Mom says her father may have had a heart arrhythmia. I know mom does. She had a procedure called a cardiac ablation, which seems to be a successful treatment. I haven’t experienced any arrhythmias yet, but wonder if any of this affects my risk. Besides my father, nothing is really clear about a family history of heart disease. And what should I discuss about this with my seven siblings?<br /><br /><strong>23andMe Heart Disease Reports Fall Under a Different Category</strong><br /><br />Information on the 86 health and traits included in the 23andMe Research Reports section reside there because they do not establish a large enough increase in risk to be included in the Clinical Reports section. For a disease to be included in Clinical Reports, the riskiest combination of genotypes must increase a person's odds of developing the condition by a factor of three or greater and elevate absolute lifetime risk to at least 5%. The Research Reports section also includes studies that still need to be confirmed by the scientific community, and includes topics where there may be contradictory evidence. The results of these studies may not be conclusive.<br /><br /><strong>Heart Attack in the Research Report Section</strong><br /><br />The heritability of death from a heart attack is estimated to be 38% for women and 57% for men. The Odds Calculator tells me my risk is 2.4 out of 100 for my age, but that risk increases more than 5 times in the next 25 years.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi2VeaXzsVAepnhNfv88HWukykt1uYeQp5UZ9zGgQSBuYpSSxvfnDaZTeKnPJy414kX5aN3NKrhSanzlLEp7wstPb23MWdWBRIDaXQT0XX1PCkEBiETrtBUSJfbiId8U5BsxET4g_lyX7L-/s1600-h/23+Odds+Calculator+Heart+Attack.JPG"><img id="BLOGGER_PHOTO_ID_5400792923299437522" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 226px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi2VeaXzsVAepnhNfv88HWukykt1uYeQp5UZ9zGgQSBuYpSSxvfnDaZTeKnPJy414kX5aN3NKrhSanzlLEp7wstPb23MWdWBRIDaXQT0XX1PCkEBiETrtBUSJfbiId8U5BsxET4g_lyX7L-/s400/23+Odds+Calculator+Heart+Attack.JPG" border="0" /></a><br /><em>Click image to enlarge</em><br /><br /><strong>It’s In the SNPs</strong><br /><br />Numerous SNPs associated with one's chances of a heart attack have been found in the chromosomal region 9p21.The reported SNP is not in a known gene, but it could affect a gene in a neighboring stretch of DNA. I think this is the first time I’ve heard that a possible pathogenic SNP is not part of a gene.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiv3nKdvuXK2l1kRY8b5SHf1XKMxtK1hFYMx5KcO8y1ZnVfEYjEwKgxySDjYC-hYRFCgYTwdxEQwwR-IQZK08kjM5lvUcN1tumKeuZ6dtU7vhLIEKZ5xaWMdqkDMR5C2jlmwQfrzmXyHfHc/s1600-h/23+Technical+Report+Heart+Attack.JPG"><img id="BLOGGER_PHOTO_ID_5400804485939944994" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 169px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiv3nKdvuXK2l1kRY8b5SHf1XKMxtK1hFYMx5KcO8y1ZnVfEYjEwKgxySDjYC-hYRFCgYTwdxEQwwR-IQZK08kjM5lvUcN1tumKeuZ6dtU7vhLIEKZ5xaWMdqkDMR5C2jlmwQfrzmXyHfHc/s400/23+Technical+Report+Heart+Attack.JPG" border="0" /></a><br /><em>Click image to enlarge</em><br /><br /><strong>What About High Blood Pressure</strong><br /><br />Let’s look at four other heart-related 23andMe reports. Left untreated, severe hypertension can lead to heart failure, stroke, vision loss or kidney problems. Environmental risk factors such as age, weight, inactivity, diet and stress can contribute to hypertension, but genetics also contributes.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjTscubmiIubfN-xoVLsgjsTkT-TMwanJfgsUXnHNAFneoCwaAozyXmtHbVKanzfmkeqBSEHmnNJkb0hl-tl889cjrMfT70x3JXOJ6DJT7hQQ-s0PVVVfvrOoyK126zQ9Qe2A1-GM-sG0Me/s1600-h/23andMe+Hypertension3.jpg"><img id="BLOGGER_PHOTO_ID_5400805141152235266" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 150px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjTscubmiIubfN-xoVLsgjsTkT-TMwanJfgsUXnHNAFneoCwaAozyXmtHbVKanzfmkeqBSEHmnNJkb0hl-tl889cjrMfT70x3JXOJ6DJT7hQQ-s0PVVVfvrOoyK126zQ9Qe2A1-GM-sG0Me/s400/23andMe+Hypertension3.jpg" border="0" /></a><br /><em>Click image to enlarge</em><br /><br />I learn from 23andMe that from several studies, with the total number of subjects of 5,500 individuals of European ancestry, each T at the SNP rs3754777 increased subjects' systolic blood pressure about 2 mm Hg and diastolic blood pressure about 1 mm Hg. This doesn’t seem to make that much of a difference. I have never been hypertensive, so I think I’m OK here.<br /><br /><strong>If I Was Prescribed Beta Blockers</strong><br /><br />Beta-blockers are given to people who have had a recent heart attack, or who have high blood pressure.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhNNkrtGFeVRZHTVWG0KSk-EkJ7kAlMVL6AsRKIKWE5jyCKuxwWSS3GmkXmpM_PRrMSc24NWqTGQ1dK3-J5E-SMji74FbXYW2Ac-EHAketWIU1519IRXK8LplktWiTTFP-JwY2WCP3oiA5E/s1600-h/23andMe+Beta+Blocker2.jpg"><img id="BLOGGER_PHOTO_ID_5400806248865702018" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 144px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhNNkrtGFeVRZHTVWG0KSk-EkJ7kAlMVL6AsRKIKWE5jyCKuxwWSS3GmkXmpM_PRrMSc24NWqTGQ1dK3-J5E-SMji74FbXYW2Ac-EHAketWIU1519IRXK8LplktWiTTFP-JwY2WCP3oiA5E/s400/23andMe+Beta+Blocker2.jpg" border="0" /></a><br /><em>Click image to enlarge</em><br /><br />After development of the beta-blocker bucindolol was halted, the authors of one study found that people with the CC genotype who were given bucindolol had a 38% reduction in mortality compared to placebo. This might be an example of using pharmacogenomics to find if certain drugs can be effective for people of a particular genotype. I may need to remember this in the future.<br /><br /><strong>Or Prescribed a Statin</strong><br /><br />Statin drugs are prescribed to reduce cholesterol levels in people who have a high risk of cardiovascular disease.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgD9SsdiqrC5mJz3qe2ID1HIFZXHMEUo6OcS7BHbaQSAuj2VyNTSa4pJ70LDHvZhL8BCaUXJjNtA6WDknjmOwwkLm9pp79d2SgMnElYpUcsN2yczM2d4fI7isoDbQHUqKj8lI2HaPWmzLuh/s1600-h/23andMe+Statin+Response2.jpg"><img id="BLOGGER_PHOTO_ID_5400807355807007714" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 136px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgD9SsdiqrC5mJz3qe2ID1HIFZXHMEUo6OcS7BHbaQSAuj2VyNTSa4pJ70LDHvZhL8BCaUXJjNtA6WDknjmOwwkLm9pp79d2SgMnElYpUcsN2yczM2d4fI7isoDbQHUqKj8lI2HaPWmzLuh/s400/23andMe+Statin+Response2.jpg" border="0" /></a><br /><em>Click image to enlarge</em><br /><br />Myopathy (experiences muscle pain and/or weakness) is a very rare side effect (one person in 10,000) of statins, even among those with genotypes that increase their odds of experiencing it. Having two C copies of the SNP increases a person's odds of myopathy by about 17 times, but the overall risk is still very small. If I’m ever prescribed a Statin, I won’t have to worry about this one-in-10,000 risk increasing. But My Problem Is Cholesterol From talking with the source of all family medical knowledge – Mom – I’m fairly convinced high cholesterol will be my problem.HDL, or high-density lipoprotein, is the “good” cholesterol that is considered protective against heart disease, and is another 23andMe ‘Research’ report.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiZl1G5KBpUvHv0hW2qDzt8k50vYckf9VE6F2PoVBs5qJhr6IgjaJJbbFF_vdJfk2r6bd5KOxvZXco2vt4jXqVzfrisw5jM-4wp4IfSUgSeACSjaSZXUjIW7Z_sKiEZJZ62Lx7yoODLIJHP/s1600-h/23andMe+HDL+cholesterol.jpg"><img id="BLOGGER_PHOTO_ID_5400807728449396098" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 249px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiZl1G5KBpUvHv0hW2qDzt8k50vYckf9VE6F2PoVBs5qJhr6IgjaJJbbFF_vdJfk2r6bd5KOxvZXco2vt4jXqVzfrisw5jM-4wp4IfSUgSeACSjaSZXUjIW7Z_sKiEZJZ62Lx7yoODLIJHP/s400/23andMe+HDL+cholesterol.jpg" border="0" /></a><br /><em>Click image to enlarge</em><br /><br />My HDL is good at 50 (normal range 40-63). But my total cholesterol has been between 267 and 295 (normal range 158-199). There is no report from 23andMe on LDL or bad cholesterol and my genotype. I would like to see this.<br /><br /><strong>Doing My Own ‘Research’</strong><br /><br />When I searched for a study on LDL levels and genetics, I found a paper titled “The novel genetic variant predisposing to coronary artery disease in the region of the PSRC1 and CELSR2 genes on chromosome 1 associates with serum cholesterol”.<br /><br />The study genotyped 2,037 adult individuals and measured their total cholesterol, high-density lipoprotein (HDL) cholesterol and glucose, blood pressure, body mass index and waist-hip ratio, for the lead SNPs in the seven CAD-associated loci. SNP rs599839, representing the locus in the vicinity of the PSRC1 and CELSR2 genes on chromosome 1p13.3, showed a strong association with total cholesterol. The association of the A allele with higher total cholesterol was confirmed in an independent cohort of 847 healthy adults, and related to an effect on low-density lipoprotein (LDL) cholesterol.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjC2PHcMnprXuzWTJZ_ItIYr7HFvH2etgNAkochchEUIedJbJF5Jz7ggSKdfASjmFyao6TC5HC4B0DEqKqB1R8p2SZgRC3O03t3EEd8DD3NxDO39VSBMI9TGj5S8AjtgG9cLq8g5aiNfr7u/s1600-h/23+raw+data+cholesterol+CAD+SNP.JPG"><img id="BLOGGER_PHOTO_ID_5400808220382822690" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 193px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjC2PHcMnprXuzWTJZ_ItIYr7HFvH2etgNAkochchEUIedJbJF5Jz7ggSKdfASjmFyao6TC5HC4B0DEqKqB1R8p2SZgRC3O03t3EEd8DD3NxDO39VSBMI9TGj5S8AjtgG9cLq8g5aiNfr7u/s400/23+raw+data+cholesterol+CAD+SNP.JPG" border="0" /></a><br /><em>Click image to enlarge</em><br /><br />When I entered SNP rs599839 into the Browse Raw Data feature of my 23andMe report, I found that I have the A allele. The study concluded that the findings support further investigation of the role of these genes in cholesterol metabolism and coronary risk. So at this point, I don’t have any analysis for my genetic risk for high total cholesterol.<br /><br /><strong>He’s Still Throwing Utah Snow</strong><br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh6nBH6KZZIGpe3mDAGOYTuMopI62RN01h9dm0onv5KJmK_0zfrsPNkkrW5dxnxQAyPESjGwcrl1KS9YWKEfOVAizYuLYvXPjpD6b1YBrP3tLOGRHBpkWQzQJuojJY8juKHGvr_5rgF2s0w/s1600-h/dad+snow+blowing.JPG"><img id="BLOGGER_PHOTO_ID_5400847882894579730" style="FLOAT: right; MARGIN: 0px 0px 10px 10px; WIDTH: 320px; CURSOR: hand; HEIGHT: 240px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh6nBH6KZZIGpe3mDAGOYTuMopI62RN01h9dm0onv5KJmK_0zfrsPNkkrW5dxnxQAyPESjGwcrl1KS9YWKEfOVAizYuLYvXPjpD6b1YBrP3tLOGRHBpkWQzQJuojJY8juKHGvr_5rgF2s0w/s320/dad+snow+blowing.JPG" border="0" /></a>Dad is still active at age 75. His favorite thing to do (besides reading my blog) is running his snow-blower multiple times a week during the winter. It's my favorite thing for him to do also. It means his ticker is still strong.<br /><br />Maybe I should ask Dad to take the 23andMe test so we could compare our 9p21 SNPs and further validate my familial risk. But the longer he hangs in there is good for me - and good for me again.<br /><br /><br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg_469ykM_xAw2HHFPI6a7bzDWZkC-sETvWb6zNEXMu_IyKFnlKDzcSX-zcvaaznr-aFqYB38P2jZXdAhgrSuYrkez4yVrDJgdLs_9-yYO11oF1dCcNV8h7WnMMPds2iMS6iUFGlRkAnILF/s1600-h/MarcSWilliams-thumb.jpg"><img id="BLOGGER_PHOTO_ID_5341272521423463202" style="FLOAT: left; MARGIN: 0px 10px 10px 0px; WIDTH: 78px; CURSOR: hand; HEIGHT: 78px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg_469ykM_xAw2HHFPI6a7bzDWZkC-sETvWb6zNEXMu_IyKFnlKDzcSX-zcvaaznr-aFqYB38P2jZXdAhgrSuYrkez4yVrDJgdLs_9-yYO11oF1dCcNV8h7WnMMPds2iMS6iUFGlRkAnILF/s320/MarcSWilliams-thumb.jpg" border="0" /></a><br /><br /><strong>Perspective from a medical geneticist</strong><br /><br /><br /><br /><strong>True confessions of the heart</strong><br /><br />As I read Grant’s post, my first thought was that I should ask one of my cardiology colleagues to write the response. His approach to this issue is a clear indication of what a motivated consumer can do to generate information about risk as well as defining ways to impact this risk. The stark reality is that cardiovascular disease of all types is the leading killer of Americans—responsible for 1 out of every 2.8 deaths in 2005.<br /><br />As opposed to many of the other conditions we’ve talked about, there are lots of preventive measures that can reduce one’s risk of coronary artery disease and hypertension including exercise, smoking cessation, weight loss, dietary changes and many classes of medication. I faithfully take a baby aspirin every night for this very reason.<br /><br />Rather than provide a “geneticist’s perspective” on Grant’s post, I’ve decided to confess my risk and behaviors following Grant’s template as I see them from my perspective as a patient who hasn’t been genotyped.<br /><br /><strong>Family History</strong><br /><br />Three of my four grandparents lived into their mid-90s. My paternal grandfather died before I was born of what I think was a hemorrhagic stroke. My recollection is my father told me he had severe hypertension and smoked—two major risk factors. Of the three that lived to a ripe old age, none had any interventions or procedures for coronary disease.<br /><br />In fact, my maternal grandfather died suddenly one day at age 96 (I presume of a cardiac arrest) after literally never being sick a day in his life. His only medication was a daily baby aspirin (which he began taking after his grandson, the medical student, suggested it might be a good idea). My mother is alive and extraordinarily active at age 83. She has no heart issues or hypertension. My father died in his 60s of mesothelioma due to asbestos exposure when he was an engineer; chalk one up for environment over genetics. He never experienced any cardiac issues although he had elevated cholesterol.<br /><br />Examination of the extended family identifies a paternal uncle who had bypass surgery in his late 60s and another with coronary artery disease in his 70s, although he died of a blood disease. Another paternal uncle had a stroke, but - like his father - smoked and had hypertension. My maternal aunt and uncle have had no cardiac issues in their 80s (and my uncle being a lifelong smoker). I find this information to be very reassuring—perhaps too much so.<br /><br /><strong>Risk of Heart Attack</strong><br /><br />While I’ve not been genotyped, according to my internist my risk for heart attack is average. This risk is based on risk assessments such as the Framingham study and the ATPIII guidelines. In my own mind, I consider myself to be at below average risk given my family history. The family history information collected by the clinical risk stratification tools noted above is rudimentary compared to my 3 generation pedigree!! I rest comfortably in my cloud of delusion and denial!<br /><br />Grant mentions the 9p21 SNP that 23andMe genotypes. This is clearly the best characterized risk predicting SNP for cardiovascular disease, although there may be as many as 10 others that independently reclassify risk for coronary artery disease (according to deCODEme’s Chief Scientific Advisor Jeffrey Gulcher.) These are not currently part of the 23andMe risk stratification.<br /><br />What is interesting and counterintuitive to me is that these genomic markers confer risk that seems to be completely independent of family history and clinical markers such as cholesterol. What is not known is whether modification of lifestyle or use of medications will attenuate the risk conferred by these genomic markers. So, no genotyping for me, at least for the present.<br /><br /><strong>High Blood Pressure</strong><br /><br />I am proud to say that I am a hypertension carrier. That is to say my presence seems to induce hypertension in others while mine remains blissfully normal (with the exception of a systolic elevation immediately prior to my recent colonoscopy but that’s a story for another day). This is in spite of a zealous aversion to regular exercise and a penchant for salt consumption that drives Janet crazy (she has hypertension that is well controlled by medications despite much better health habits). So, no issues here (nor as best as I can determine for any of my 1st or 2nd degree relatives).<br /><br />This does bring up an interesting point relative to 23andMe—if I have my blood pressure checked regularly, does my rs3754777 genotype status really matter? Would I do anything differently based on my genotype status? I think not. I would like to think that if my blood pressure was elevated it would lead to modifications in my life, at least to the extent of taking a medication.<br /><br /><strong>Cholesterol</strong><br /><br />Lest you think that my heart will never give out, I will confess that cholesterol is an issue for me (and for my father, daughter and my mother to a lesser degree). My total cholesterol is elevated (last value was 235) with a borderline HDL of 40 and an elevated LDL of 179. I do drink a glass of red wine every evening, but this does not appear to elevate my HDL significantly L. I think I’ll continue this anyway.<br /><br />I actually took a statin medication for a couple of years with a spectacular impact on my numbers (total cholesterol of 141, HDL 37 and LDL of 88). I experienced no problems with the drug including no muscle symptoms and normal liver function studies. A couple of years ago I lost a significant amount of weight and my internist and I decided to see how this impacted my numbers. It had a beneficial effect with a total cholesterol of 206 and LDL of 152—not perfect, but probably adequate to stay off statins. Of course my weight has crept up since the low point leading to worsening of my numbers. So, should I try to lose weight again (almost certainly yes) or should I go back on a statin given my excellent clinical response and tolerance? (Again, probably yes).<br /><br />The reality is that I should probably do both given the increasing evidence of benefit of statins for a number of circumstances. I am deleted for the medication aversion gene located on the Y chromosome, so compliance has never been an issue. I would not pursue genotyping given that I’ve tolerated the drugs in the past.<br /><br />Given the importance of statins in the treatment armamentarium, I would argue that given the rarity of severe reactions to statins, genotyping could lead to harm if an individual chose not to take a statin based on an increased risk of a reaction given that most individuals with the ‘at risk’ genotype would still tolerate the medication just fine. My mother, in contrast, developed muscle aches with every statin she tried so despite her mild cholesterol abnormalities, she has elected not to take these drugs and I wholeheartedly agree. Besides, living to 83 without any heart problems is probably telling us more about her risk than any test, genetic or otherwise.<br /><br />I did want to comment on a functionality of 23andMe that we’ve not explored before. Grant did extensive research about factors that influence cholesterol levels and identified information about genetic factors. He was able to enter these into the raw data browser and retrieve his genomic status. This clearly demonstrates how a sophisticated and highly motivated consumer can go beyond what is presented by the testing service. As to how it will alter Grant’s health behavior, well that’s up to him isn’t it?<br /><br /><strong>My Health Behavior</strong><br /><br />We all have our beliefs about health and wellness. I somewhat facetiously make two statements about exercise and eating well: 1) Regular exercise does lead to longer life, but you only extend life by how much time you have spent exercising. Stated another way, if you exercise you will live longer but you will have spent all your extra time exercising!! 2) I also believe that eating a healthy diet doesn’t help you live longer, however it will seem a lot longer. Verily my epitaph will read, “He died in search of the perfect bacon cheeseburger.” I also believe that mental well-being and stress reduction are strongly protective despite a dearth of evidence. Therefore, my music making, art business and golf take up the time that I could otherwise devote to exercise. However, I think that if I substituted exercise for these activities I would be substantially less happy.<br /><br />So, I admit I’m not the best role model for healthy behaviors as we currently understand them. I would like to believe that if there was compelling information, genotypic or not, that I would use this to modify my health behaviors. Realistically, I think it may take a more significant event, i.e. a heart attack, for me to be more serious about these issues. Not the most intelligent approach given the high percentage of men that don’t survive their first MI.<br /><br />There is another reality which is that no one gets out alive!! All of us will die of something (the Life Extension Institute’s beliefs to the contrary) so would dropping dead of a heart attack be so bad compared to a lingering chronic disease like cancer or my personal worst nightmare-dementia? Not in my mind, but then the choice isn’t all mine is it?Grant M. Woodhttp://www.blogger.com/profile/18185402177712853914noreply@blogger.com2tag:blogger.com,1999:blog-1887866819730206489.post-13860097059607267412009-10-19T06:45:00.001-06:002009-10-19T12:54:01.670-06:00Do You Know Alpha-1 Antitrypsin Deficiency?Let me confess this upfront. Until I met John Walsh at the <a href="http://www.geneticalliance.org/conf08">2008 Genetic Alliance conference</a>, I was not familiar with the genetic disorder called <a href="http://www.alpha1.org/">Alpha-1 Antitrypsin Deficiency </a>(AATD). John is one of the founders and President of <a href="http://alphanet.org/">AlphaNet</a>. Since then I have learned that AATD, a genetic mutation, reduces the levels of a protective protein in the bloodstream. AAT deficiency can lead to chronic obstructive pulmonary disease (COPD), specifically emphysema, and liver disease.<br /><br />John had attended a <a href="http://geneticalliance.org/ws_display.asp?filter=conf08.workshop.electronic.health">presentation</a> I gave on improving the use of family health history and genetic/genomic data in the electronic health record. Later I was both surprised and honored when he invited me to become a member the AlphaNet board of directors. So when I saw that Alpha-1 Antitrypsin Deficiency was added in April of this year to my <a href="https://www.23andme.com/">23andMe</a> Carrier Status report, I thought the timing was providential.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEijH6Q24Gvm51I_bbDHJvLWy28rH4Ur3ytyNnlIGfwhctiZGJ-wfOWH6bT_UehMyvzLes2mYpIyUqFGLqBGltfrxYlX8EXpbZaUGeEo1_9FkzrjYU5_4UlM5VLmt-4PBaiugezthax0OpoE/s1600-h/23+carrier+status+3.jpg"><img id="BLOGGER_PHOTO_ID_5394159250473505026" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 287px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEijH6Q24Gvm51I_bbDHJvLWy28rH4Ur3ytyNnlIGfwhctiZGJ-wfOWH6bT_UehMyvzLes2mYpIyUqFGLqBGltfrxYlX8EXpbZaUGeEo1_9FkzrjYU5_4UlM5VLmt-4PBaiugezthax0OpoE/s800/23+carrier+status+3.jpg" border="0" /></a><br /><em><span style="font-size:85%;">Click image to enlarge</span></em><br /><br />As I have new opportunities to met people with Alpha-1, they would always ask if I have been tested to see if have the mutation. I hadn’t until the 23andMe result appeared. The test most people take is a simple <a href="http://www.alphaone.org/alphas/?c=02-Get-Tested">finger-stick test for blood</a>. But you can also get tested by genotyping, which is how I learned of my AAT deficiency carrier status.<br /><br />23andMe told me that an estimated one out of every 5,000 - 7,000 North Americans has AAT deficiency. Interestingly, <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Search&db=pubmed&term=18565211">in Scandinavia the numbers are higher</a>. One in every 1,500 to 3,000 people there is affected. These numbers go higher when you take into account the people who have AAT deficiency, but have not been diagnosed.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjnTqDcQmd02JLNIhbj5-dxaYA83CPkaQa6n40vljmQoB8FRdXN14gKIwyf9n5YhwSB66231SsILhL8iSbX1O5XQfDq7ZQXr9ekP4cAVUJfbhHXnr28g_FpPWlv6fmCDXMW-mKfEJHvkVq4/s1600-h/23+Genes+vs+Environment+Alpha1.JPG"><img id="BLOGGER_PHOTO_ID_5394159907530193538" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 286px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjnTqDcQmd02JLNIhbj5-dxaYA83CPkaQa6n40vljmQoB8FRdXN14gKIwyf9n5YhwSB66231SsILhL8iSbX1O5XQfDq7ZQXr9ekP4cAVUJfbhHXnr28g_FpPWlv6fmCDXMW-mKfEJHvkVq4/s800/23+Genes+vs+Environment+Alpha1.JPG" border="0" /></a><br /><em><span style="font-size:85%;">Click on image to enlarge</span></em><br /><br />The main versions of the gene that encodes AATD are PI*M (the normal version), PI*S, and PI*Z. A person inherits a copy of the gene from each parent, producing six possible combinations: MM, MS, MZ, SS, SZ, and ZZ. Something I learned from 23andme - In addition to the PI*M, PI*S, and PI*Z versions of the gene for AAT, there are more than 20 known rare mutations that can lead to AAT deficiency.<br /><br />The PI*Z form of the gene is the most severe mutation; the ZZ genotype accounts for 95% of AAT deficiency. People with the SZ genotype are at an increased risk for COPD, particularly if they smoke. The MZ genotype causes only mild reduction in AAT protein levels, but may lead to decreased lung function in smokers.<br /><br /><strong>Difficult Diagnosis</strong><br /><br />The AlphaNet website tells us that Alpha-1 patients experience difficulty and delay in getting properly diagnosed. Clinical research studies have shown that once a patient develops symptoms, it takes an average of seven years and visits to five different doctors before the diagnosis of Alpha-1 is correctly made. I have met Alpha’s that confirm this. Many non-smoking Alpha’s are of accused of smoking by their doctor. About 3% of all people diagnosed with COPD may have undetected Alpha-1.<br /><br />For treatment of lung disease caused by AAT deficiency, intravenous alpha-1-antitrypsin augmentation therapy, annual flu vaccination and a pneumococcal vaccine every 5 years are recommended. Relief of breathlessness may be obtained with long-acting bronchodilators and inhaled corticosteroids. Both end-stage lung and liver disease can be treated by organ transplantation. In AATD patients with cirrhosis of the liver, the prognosis is generally grave.<br /><br /><strong>The AlphaNet Community</strong><br /><br /><a href="http://www.alphanet.org/file_download/65">I began working</a> with AlphaNet a year ago. I learned that one of the many things AlphaNet does is provide disease care coordinators for more than 7,000 people with Alpha-1. Their website further explains that “AlphaNet Coordinators are spread across the United States and subscribers to AlphaNet are assigned to a specific AlphaNet Coordinator based upon geographical location. Each AlphaNet subscriber is contacted at least monthly by his or her AlphaNet Coordinator. The AlphaNet Coordinator provides support, education and assistance with augmentation therapy infusion issues and supplies.” Since 1997, AlphaNet has donated $25 million to the <a href="http://www.alpha1.org/">Alpha-1 Foundation</a>, which performs research to cure AAT deficiency.<br /><br />More information I learn from 23andMe includes -<br /><br />· Not everyone with AAT deficiency will have symptoms, leading some researchers to suggest that additional genetic factors other than mutations in the gene that encodes AAT may be involved.<br />· Between 15% and 19% of adults with AAT deficiency develops cirrhosis of the liver after age 50.<br />· The donor liver following liver transplantation will make normal AAT protein and actually cure the deficiency in the rest of the body.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhxXoNErk1EPT-CTqM7tLOgVkVSGy-G1pNCxkgS41RzRqwp1C636plnhUKgl78DR8X2TM_zKVS5Em4tROqGIWO74SFm5CQ3fRAmG-H4AL0KSX0MqXr1KeNWhXvWMBHnqaSnlowxYB2XPY1b/s1600-h/23+Technical+Report+2+Alpha-1.JPG"><img id="BLOGGER_PHOTO_ID_5394161203568346530" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 227px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhxXoNErk1EPT-CTqM7tLOgVkVSGy-G1pNCxkgS41RzRqwp1C636plnhUKgl78DR8X2TM_zKVS5Em4tROqGIWO74SFm5CQ3fRAmG-H4AL0KSX0MqXr1KeNWhXvWMBHnqaSnlowxYB2XPY1b/s800/23+Technical+Report+2+Alpha-1.JPG" border="0" /></a><br /><em><span style="font-size:85%;">Click on image to enlarge</span></em><br /><br /><strong>Family History</strong><br /><br />A paper on Alpha-1 antitrypsin deficiency was published this summer in the <a href="http://content.nejm.org/cgi/content/short/360/26/2749">New England Journal of Medicine</a>. One of the authors, Dr. Robert A. Sandhaus, is also a board member and Medical Director of AlphaNet. The article states that “AAT deficiency is recognized in less than 10% of persons in whom a diagnosis would be expected on the basis of screening studies in the general population. The diagnosis of AAT deficiency is generally made after the identification of COPD or liver disease or after the deficiency has been diagnosed in a family member”.<br /><br />The authors recommend that a family testing discussion be held in the initial evaluation of the newly diagnosed patient. A diagnosis of Alpha-1 could impact family including brothers, sisters, children, grandchildren, and possibly extended family members.<br /><br />To assist in finding those who are still undiagnosed, Intermountain Healthcare’s <a href="http://intermountainhealthcare.org/genetics/">Clinical Genetics Institute</a> is designing a study using an internet-based, patient-entered family health history program. Both the software program and the research study are under development, but we hope to find that computerized family health history tools can be effective screening methods to identify and treat those families that might be at risk for an inherited, familial disease for which they are not aware. The earlier the detection, the less damage the disease will have done.<br /><p><br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg_469ykM_xAw2HHFPI6a7bzDWZkC-sETvWb6zNEXMu_IyKFnlKDzcSX-zcvaaznr-aFqYB38P2jZXdAhgrSuYrkez4yVrDJgdLs_9-yYO11oF1dCcNV8h7WnMMPds2iMS6iUFGlRkAnILF/s1600-h/MarcSWilliams-thumb.jpg"><img id="BLOGGER_PHOTO_ID_5341272521423463202" style="FLOAT: left; MARGIN: 0px 10px 10px 0px; WIDTH: 78px; CURSOR: hand; HEIGHT: 78px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg_469ykM_xAw2HHFPI6a7bzDWZkC-sETvWb6zNEXMu_IyKFnlKDzcSX-zcvaaznr-aFqYB38P2jZXdAhgrSuYrkez4yVrDJgdLs_9-yYO11oF1dCcNV8h7WnMMPds2iMS6iUFGlRkAnILF/s320/MarcSWilliams-thumb.jpg" border="0" /></a><br /><br /><strong>Perspective from a medical geneticist</strong><br /><br /><br /><br /><strong>Traditional vs. Predisposition Genetic Testing</strong><br /><br />The two results from testing discussed this month, BRCA and alpha-1 antitrypsin (AAT), represent much more traditional types of genetic testing than the predisposition testing we’ve written about in most of the posts. In contrast to the BRCA testing which was limited to only three mutations (or the Cystic Fibrosis gene CFTR where only one mutation is tested), the AAT test results report all of the recommended clinically important mutations in this gene. Grant does an excellent job of describing the disease and its implications.<br /><br />From my perspective, the challenge that hasn’t been adequately met in practice is testing of individuals who are symptomatic. As Grant points out, we are not doing a very good job of identifying the disease in symptomatic individuals. In 2008, Hogarth and Rachelefsky published a review in the journal Chest that looked at testing and screening for AAT deficiency. (reference below) They highlight 4 interventions that could be used if the disease was identified early. These include: smoking prevention/cessation; minimizing the hazards of occupational respiratory pollutants; the opportunities to receive augmentation therapy; and the potential for family planning and guided genetic counseling/testing. Thus we have a situation where we can definitively characterize the results of the mutation testing; we can identify individuals at risk; we can initiate preventive measures in those at risk and start treatment in symptomatic patients. This in some ways represents an ideal genetic test.<br /><br /><strong>Genetic Testing for Symptomatic Patients</strong></p><p>While there have been some suggestions that population screening (at least in Caucasians) for AAT mutations would be beneficial, the consensus has been that this approach would be too expensive. In addition, there are many individuals who carry disease causing mutations who never develop symptoms. That said, we’re doing a very poor job testing individuals who are symptomatic, despite professional guidelines supported by strong evidence that recommend testing all individuals with emphysema, COPD, or asthma with airflow obstruction not completely reversible with the use of bronchodilators; all individuals with unexplained liver disease; asymptomatic subjects with persistent obstruction found on pulmonary function test findings and with identifiable risk factors; and adults with necrotizing panniculitis.<br /><br /><strong>Informed Consumers</strong></p><p>So it certainly appears that there would be a role for informed consumers to be able to access testing given that health care professionals are not doing an adequate job. Interestingly this has been studied in AAT, including testing of minors. (see references below). These tests seem to be well accepted. Nearly 80% of current smokers indicated that they were highly likely to stop smoking if they were ZZ. Most individuals (but not all) said they would share the results of testing with their physician, however a small number would not want the result placed in their medical record because of concerns about privacy.<br /><br />The <a href="http://www.aatregistry.org/Testing.htm">U.S. Center for AIR</a> is performing testing under a research protocol to learn more about the risks and benefits of direct-to-consumer testing for AAT deficiency. This type of research is extremely important to better understand the role of consumer directed genetic testing. Kudos to the groups that are sponsoring this important research. Testing is also available outside of a research protocol through the AAT Deficiency Testing Center. In contrast to 23andMe that provides results, but no other support, AAT testing is sponsored by AAT organizations that can provide support for newly diagnosed patients.<br /><br />It should be noted that one can also measure the level of alpha 1 antitrypsin activity in the blood stream, obviating the need for a genetic test. So, if you’re interested in being tested for AAT deficiency, probably better to use one of these services than 23andMe. However, if you have been identified as carrying a mutation through the 23andMe testing, contact one of the advocacy organizations for more information. It could save your life!<br /><br /><strong>References:</strong><br /><br />Hogarth DK, Rachelefsky G. Screening and familial testing of patients for alpha 1-antitrypsin deficiency. <a href="http://www.ncbi.nlm.nih.gov/pubmed/18398118">Chest. 2008 Apr;133(4):981-8</a><br /><br />Strange, C, Moseley, MA, Jones, Y, et al Genetic testing of minors for α1-antitrypsin deficiency. <a href="http://www.ncbi.nlm.nih.gov/pubmed/16651497">Arch Pediatr Adolesc Med 2006;160,531-534</a><br /><br />Gitter AC, Jones Y, Schwartz L, et al. Confidential home α1-antitrypsin testing: specialty center support for rare diseases. Presented at: the American Thoracic Society Annual Meeting; May 18–23, 2007; San Francisco, CA; poster A988<br /><br />Strange, C, Dickson, R, Carter, C, et al Genetic testing for alpha1-antitrypsin deficiency. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15266208">Genet Med 2004;6,204-210<br /></a></p>Grant M. Woodhttp://www.blogger.com/profile/18185402177712853914noreply@blogger.com14tag:blogger.com,1999:blog-1887866819730206489.post-47095857911861947582009-10-05T08:45:00.011-06:002009-10-19T00:13:10.382-06:00Can Men Understand BRCA?I was surprised when <a href="https://www.23andme.com/">23andMe</a> added selected BRCA cancer mutations to the Carrier Status list in February of 2009, especially since everybody knows that <a href="http://www.myriad.com/">Myriad Genetics</a> holds a controversial patent to the BRCA1 and BRCA2 genes. Because Myriad is a Salt Lake City-based company, we watch them closely. And more importantly, I have a personal story with Myriad BRCA testing and a family member - which I will share at the end of this post.<br /><br /><strong>The UPDB</strong><br /><br />Myriad originated in 1991 as a gene discovery company. Their researchers were able to access and link important genealogical and medical databases, which resulted in discovering the BRCA genes. The new database was named <a href="http://www.hci.utah.edu/groups/ppr/">The Utah Population Database</a> (UPDB). It originally contained information on 200,000 Mormon family groups and most of the1.6 million descendants of the initial 10,000 Utah settlers. This database was linked to the Utah Cancer Registry (which contains more than 100,000 entries), in which generated 40,000 cross-linked entries. Since then, the database has expanded with updated genealogical and public health records, and Intermountain Healthcare has linked its clinical data with the UPDB to offer an even more powerful research tool.<br /><br /><strong>Anything Here for Me?</strong><br /><br />My 23andMe report cautions me to remember that the BRCA mutations covered by the report are only three of hundreds in the BRCA1 and BRCA2 genes that can cause cancer. The absence of these mutations does however not rule out the possibility that I may carry another cancer-causing variation in one of the other genes.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEizSex3urHR8DPRbAekI2TR1m13CNXS9Cb-EAcEvUCUP_6sWus1e2o8-xUdBNY0_zFMVkbL7VemHSIHchnc3-yRm6Qqyi9ejnyyTdRx6P7M3vwe78WpMSlDC6pwtPXbr0RmFQwJy8nMVJWD/s1600-h/23+Genes+vs+Environment+BRCA.JPG"><img id="BLOGGER_PHOTO_ID_5388948376426199938" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 365px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEizSex3urHR8DPRbAekI2TR1m13CNXS9Cb-EAcEvUCUP_6sWus1e2o8-xUdBNY0_zFMVkbL7VemHSIHchnc3-yRm6Qqyi9ejnyyTdRx6P7M3vwe78WpMSlDC6pwtPXbr0RmFQwJy8nMVJWD/s800/23+Genes+vs+Environment+BRCA.JPG" border="0" /></a><br /><em>Click on image to enlarge<br /></em><br /><br /><strong>Population Risk</strong><br /><br />It seems like a small number when one reads that only 5 to 10 percent of breast cancers occur in women with a genetic predisposition for the disease. The incidence in men only accounts for 1% of all breast cancer. In addition, I learn that these mutations greatly increase not only the risk for breast cancer in women, but also the risk for ovarian cancer in women as well as <a href="http://exploringmygenes.blogspot.com/2009/08/big-pc-what-men-fear-most.html">prostate cancer </a>among men. Additionally, 23andMe provides data for only three specific cancer-associated mutations that are found mainly in people with Ashkenazi Jewish ancestry.<br /><br />Since I am not a woman, nor an Ashkenazi Jew (100% European according to my 23andme ancestry painting), is any of this information important to me? I think so. Because I am not a carrier, the children I may have will be at reduced risk of breast cancer. But my interest at this moment is not for me, but rather for <a href="http://www.news8austin.com/shared/video/video_pop.asp?destlist=72106">affected family members</a>, for whom I care deeply.<br /><br /><strong>October is Breast Cancer Awareness Month</strong><br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhQs_ewuEb-Tl71aiBv5YXCCYOA1U5-ImIVHdTxlWN7YIC8gkCvTJCaSRAnfDnbjN-F9sRaRnPCQWxctQYXcwOb5BpFfHGVvKgHyOigSDEtfQ-4L8jmVpffTfN96gGgkaHzBrRy43_WxQNm/s1600-h/NBCAM+25+years.JPG"><img id="BLOGGER_PHOTO_ID_5388983816634082706" style="FLOAT: left; MARGIN: 0px 10px 10px 0px; WIDTH: 160px; CURSOR: hand; HEIGHT: 200px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhQs_ewuEb-Tl71aiBv5YXCCYOA1U5-ImIVHdTxlWN7YIC8gkCvTJCaSRAnfDnbjN-F9sRaRnPCQWxctQYXcwOb5BpFfHGVvKgHyOigSDEtfQ-4L8jmVpffTfN96gGgkaHzBrRy43_WxQNm/s200/NBCAM+25+years.JPG" border="0" /></a><a href="http://www.nbcam.org/">The National Breast Cancer Awareness Month</a> (NBCAM) program is dedicated to promoting the importance of early screening and detection of breast cancer through a nationwide campaign held during the month of October. They are celebrating their 25th anniversary. Whenever I hear about a NBCAM activity, I think about what my sister-in-law (SIL) went through. She is a breast cancer survivor.<br /><br /><strong>A Personal Story</strong><br /><br />Her story starts with her maternal Grandma, who was diagnosed with breast cancer at age 45. After several surgeries failed to “hack it out”, Grandma died at 49.<br /><br />My SIL’s mother was first diagnosed with breast cancer at age 29. She had surgery to remove her breasts, followed by chemotherapy, but that didn’t stop the cancer from spreading to her spine, and finally her lungs. Even after complaining about respiratory difficulties, the lung cancer was not discovered until the autopsy. Mom also fought for 4 years before dying. My sister-in-law was seven years old.<br /><br /><strong>Thinking It Was Inevitable</strong><br /><br />While growing up, my SIL always thought that at some point she would die of breast cancer herself. In 2001 when she was 25 years old, she heard about the Myriad BRCA test and wanted to take it. The test came back negative for any of the BRCA mutations, so she started to think she had dodged a bullet. She did have genetic counseling, which would have told her some risk still existed. She saw an oncologist, but did not have a mammogram since she was nursing a newborn at the time.<br /><br />Three years after the negative Myriad test, my SIL was pregnant once again, and for the first time ever, found a lump in her breast. She had an ultrasound and was told that the lump was benign and would disappear after the pregnancy. Two weeks later she visited her Obstetrician and told the doctor she thought the lump was getting bigger. A needle biopsy by a breast surgeon revealed she had cancer.<br /><br /><strong>A Prayer Is Answered</strong><br /><br />A small miracle followed. She began chemotherapy while pregnant with her fourth child. Her daughter was born as beautiful and healthy as her other children. After the birth she had a radical bi-lateral mastectomy, reconstruction, and radiation therapy.<br /><br />I asked her if she felt modern medicine had let her down. She said no, because – she explained - she had always felt that it was her responsibility to follow through with the accurate diagnosis and treatment of her healthcare. However, she did feel that she should have asked an aunt to take the BRCA test to help interpret her results. Today, she is still interested in learning about new genetic testing for breast cancer that might help her three young daughters.<br /><br />As their Uncle, these three beautiful little angels give me sweet hugs and a lot of love. As I thought about their future and possible inherited risk, I found myself feeling sad thinking about what they might face in the future. I can’t imagine how I would feel if I were their mother or father.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg5thXQ6wHs_OATtsXM_Xhyphenhyphenit8FJeyt38FXsDHz_the6iWNOU4VqEuprIBIVS03SvFzUtqDZzFtZ1Se7xldRETYFEFgta3NbuhlcqBun3RqfMA6OIUVdzcD_B6HS1i8px5tCLhV3qHv3344/s1600-h/Janet+A+001-1.jpg"><img id="BLOGGER_PHOTO_ID_5363017094122700610" style="FLOAT: left; MARGIN: 0px 10px 10px 0px; WIDTH: 89px; CURSOR: hand; HEIGHT: 100px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg5thXQ6wHs_OATtsXM_Xhyphenhyphenit8FJeyt38FXsDHz_the6iWNOU4VqEuprIBIVS03SvFzUtqDZzFtZ1Se7xldRETYFEFgta3NbuhlcqBun3RqfMA6OIUVdzcD_B6HS1i8px5tCLhV3qHv3344/s200/Janet+A+001-1.jpg" border="0" /></a><br /><strong><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjUC1pRX2YY0sOHY4eYu7Qh-rsRksUQ71kXpKIgMb666WCyj7GSRaygHe-ip7xwDcGTwL-SxD73CbdPo1XEwxh_qvfu1BCmgKEPhskcd00biSmwGvjELsU2vzvYvKREPP2hPF_OeSe8GEce/s1600-h/jwilliams.jpg"></a></strong><br /><strong>Perspective from a Certified Genetic Counselor</strong><br /><br /><br /><strong></strong><br /><strong></strong><br /><strong>BRCA Mutations and Inherited Risk for Breast Cancer </strong><br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgL10NvulNNq8qjJeyDQwAco3zJ85CdhYjZwUKGKVjCEKVpvSlaSPein5BcTI4dJhYzcMepVaBmgDnKfua010B8UWT7WqMngUWewmJVfp1hMGQllOKhPiD-zkyLbLy8yZd6kRiwGcJMOWVO/s1600-h/ribbon.JPG"><img id="BLOGGER_PHOTO_ID_5388989495339898850" style="FLOAT: left; MARGIN: 0px 10px 10px 0px; WIDTH: 72px; CURSOR: hand; HEIGHT: 114px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgL10NvulNNq8qjJeyDQwAco3zJ85CdhYjZwUKGKVjCEKVpvSlaSPein5BcTI4dJhYzcMepVaBmgDnKfua010B8UWT7WqMngUWewmJVfp1hMGQllOKhPiD-zkyLbLy8yZd6kRiwGcJMOWVO/s200/ribbon.JPG" border="0" /></a><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi96A8kx4rrGJwpzEZZutOGpagLkKInPucfBhcSukrQf0lPRKOrNmwU5yWWAIMToj06rZtZbdUvZk9VhvFAj5GTZsbTQbmmumMSJuynhpqdm01yoFCr1hbJgghAFof4Aoh9UUMUMWY-0xHO/s1600-h/ribbon.JPG"><img id="BLOGGER_PHOTO_ID_5388989183142713538" style="FLOAT: left; MARGIN: 0px 10px 10px 0px; WIDTH: 72px; CURSOR: hand; HEIGHT: 114px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi96A8kx4rrGJwpzEZZutOGpagLkKInPucfBhcSukrQf0lPRKOrNmwU5yWWAIMToj06rZtZbdUvZk9VhvFAj5GTZsbTQbmmumMSJuynhpqdm01yoFCr1hbJgghAFof4Aoh9UUMUMWY-0xHO/s200/ribbon.JPG" border="0" /></a><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg6Ek8tdxLaTCUFS7ewfbg-1zaFbKTanz5pC57EjED6b_KR-6-2CjrZRpVG38kg7k5AOZ93logO_IfEdSVQrx2t7JRW72Hkv7EyCQApzQ-Dm3ibYp0UGCuaFRvtf7mejlFHBIwtabRAMohc/s1600-h/ribbon.JPG"><img id="BLOGGER_PHOTO_ID_5388988689373154898" style="FLOAT: left; MARGIN: 0px 10px 10px 0px; WIDTH: 72px; CURSOR: hand; HEIGHT: 114px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg6Ek8tdxLaTCUFS7ewfbg-1zaFbKTanz5pC57EjED6b_KR-6-2CjrZRpVG38kg7k5AOZ93logO_IfEdSVQrx2t7JRW72Hkv7EyCQApzQ-Dm3ibYp0UGCuaFRvtf7mejlFHBIwtabRAMohc/s200/ribbon.JPG" border="0" /></a><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj1qWSb0cR4sCMYvwFLmjcGN5ZaWpfBhalud0pWuHDiRCilD8L8iKaWuyR-pZwFqFF69Bc844l4cYam39_1YfSriFeLURr1JILTqJRse1PbdpCmi1FvEeLAmQScYGFiW9pl8ETyiQcm3vfz/s1600-h/ribbon.JPG"><img id="BLOGGER_PHOTO_ID_5388986453667556354" style="FLOAT: left; MARGIN: 0px 10px 10px 0px; WIDTH: 72px; CURSOR: hand; HEIGHT: 114px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj1qWSb0cR4sCMYvwFLmjcGN5ZaWpfBhalud0pWuHDiRCilD8L8iKaWuyR-pZwFqFF69Bc844l4cYam39_1YfSriFeLURr1JILTqJRse1PbdpCmi1FvEeLAmQScYGFiW9pl8ETyiQcm3vfz/s200/ribbon.JPG" border="0" /></a><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgmrnkwO7BqxIIUXuTp4_xHB_IDwuY5mzBRWhXZpqmBUyA0he6rtwpixiJEKaqHW5U_YdEL6yZgcXYTuVymB9-syC7lWeUI-Luvs65V-PLdqBD1ZFvZBE3FoztcfpDNHcBHd70Lw0UcKUF4/s1600-h/ribbon.JPG"></a> <a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhmG3_JMJViqX-2gQMYPBtZDHypqg782jil-rBmsfa_Ng0AUsDbfvUEIAGfBigTrulNKVsOFuhTL5iX9yhXWbn4ysgeVQowT9fIPqJ15UcL38KZ_g7aQAu4N3SrtYZkxg4eGRV6uNimsjfA/s1600-h/ribbon.JPG"></a><br /><br /><br /><br /><br /><br /><br /><br />Women who talk with me about inherited risk for breast cancer often ask about “the breast cancer gene”. I think it comes as a surprise to many of these women (and their husbands) that everyone, men and women, have BRCA genes. In fact, every person has two copies each of BRCA1 and BRCA2. One of each came via the egg cell from their mother, and one came in the sperm cell donated by their father that resulted in their personal conception; talk about personalized health! So although Grant does not carry one of the three common Ashkenazi (or Eastern European) Jewish BRCA mutations, he does carry BRCA genes in which hundreds of mutations are possible. Cheery thought!<br /><br />Grant shared the story of his sister-in-law and her family’s experience with relentless breast cancer. Breast cancer at ages 45, 29, and 28 are the hallmark of hereditary breast cancer caused by a BRCA mutation. How could it be that Grant’s sister-in-law tested negative for BRCA mutations and then she was diagnosed with breast cancer? Her story helps to illustrate the promise and the pitfalls of genetic and genomic testing, and it is a good example of how genetic test results may be only part of the story of risk. I appreciate her willingness to have her brother-in-law share her story. (I hope he told her he was sharing the story!)<br /><br /><strong>Mutation:</strong> <em>A gene mutation is a permanent change in the DNA sequence that makes up a gene. Mutations range in size from a single DNA building block (DNA base) to a large segment of a chromosome.</em><br /><br />The genomic test result that Grant received as part of 23andMe represents the mutations tested for during initial testing usually offered to individuals with Eastern European Jewish ancestry who have a family history of breast or ovarian cancer. I am not sure what led the designers of the 23andMe to select and report on BRCA mutations despite the fact that another company owns the patent for those genes. I suspect it may be because other labs have been licensed to conduct screening for the three mutations in certain specific populations.<br /><br /><strong>Promise and Pitfall</strong><br /><br />I have the sense that Grant was not surprised to learn he is not a carrier of a BRCA mutation. I have not heard him mention or write about cancer in his biologic family. That is little consolation for the fact that his sister-in-law has developed breast cancer and his nieces (grandnieces, etc.) could develop breast cancer. The promise with genetic testing is the possibility that knowing if you are at risk, it may offer the opportunity to prevent cancer. The pitfall is the false hope that testing that is negative (no mutation detected) has ruled out risk for the disease.<br /><br />As Grant’ s sister-in-law mentioned in her reflection, she wished that her aunt had been tested for BRCA mutations to help to interpret her results. If her aunt (her mother’s sister) had breast cancer and tested negative, then her negative result would have been meaningless. It would have indicated the fact that the cause of early breast cancer in the family had not yet been linked to a BRCA mutation. In the study of families with inherited breast and ovarian cancer, we know that BRCA is not the only reason for cancer in every family. There must be other hereditary factors besides BRCA that cause breast cancer. Researchers have not been able to identify another familial breast and ovarian cancer gene with the same dramatic impact of BRCA1 and BRCA2, but others or combinations of others must exist.<br /><br /><strong>The Story Is Not Over</strong><br /><br />In the same way that 23andMe updates risk assessments as new SNPS are linked to diseases and reported back to Grant, new ways to evaluate BRCA genes have been added to the analysis in high risk families. The story of Grant’s sister-in-law and her genetic testing is not over. In 2001 - and again in 2007 - Myriad Genetics updated their analysis of BRCA genes to include evaluation for large gene rearrangements.<br /><br />While rearrangements are also called mutations, the original testing for mutations involved sequence analysis of the genes and did not reveal that chunks of DNA could be missing (deleted) or copied more than once (duplicated). Several families, in whom a BRCA mutation was not originally detected, have since been found to have a duplication, or - more likely - a deletion. Grant’s sister-in-law could visit with a genetic counselor about this new testing option. The original result would inform the genetic counselor of the testing completed at the time of the test in 2001. There would not be a need to repeat the sequence test that was performed, but new analysis to look for a large rearrangement of BRCA1 or BRCA2 may provide the genetic key that would allow identification of at risk family members.<br /><br />The promise of genetic testing is realized in the identification of those at increased risk. Individuals and their family members may use this information to attend carefully to the possibility of the development of cancer at younger than expected ages. It may also allow for early intervention in those at risk when preventive interventions are available.<br /><br /><strong>Good resources for breast cancer information:</strong><br /><br />American Cancer Society: <a href="http://www.cancer.org/">http://www.cancer.org/</a><br />Susan G. Komen: <a href="http://www.komen.org/">http://www.komen.org/</a><br />Facing Our Risk of Cancer Empowered: <a href="http://www.facingourrisk.org/">http://www.facingourrisk.org/</a><br />National Cancer Institute: <a href="http://www.cancer.gov/">http://www.cancer.gov/</a>Grant M. Woodhttp://www.blogger.com/profile/18185402177712853914noreply@blogger.com3tag:blogger.com,1999:blog-1887866819730206489.post-36748909975911954952009-09-21T06:45:00.007-06:002009-09-21T20:31:39.943-06:00The Risk Type I Have For Diabetes<div><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgUbH_zodDZNiCoX56sdh4ugmALcBsIgm6FDXGPD9TvgAObl8Gi4bcBCtPVpl3TvfHG3bsKvvBZ4HLFY4DNPnycPJBO3Bcy29Lz_2gfE3c9cIexN2dmv6UWGbpsOJKuxlbRB1-bigGdU-zv/s1600-h/folate+bottle.jpg"></a><br /><br /><div>From the list of 10 diseases that <a href="https://www.23andme.com/">23andMe</a> reports on, three were listed in the Elevated Risk category. We have already posted on <a href="http://exploringmygenes.blogspot.com/2009/07/grand-opening-looking-inside-my-genetic.html">Crohn’s disease</a> and <a href="http://exploringmygenes.blogspot.com/2009/08/big-pc-what-men-fear-most.html">Prostate cancer</a>. The remaining one is <a href="http://en.wikipedia.org/wiki/Type_1_diabetes">Type I Diabetes</a>. I am lucky that I do not suffer from any of these conditions, but I value the opportunity this experience has given me to learn about them, what my risks might be, what can I do about it, and what should I discuss with my doctor if symptoms arise.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEigSIpPzsFmgtjAgeO-UXjiR4QhWbqdy8b1TonmDpmsEzfbeM9wAs8YRCbsE0v9TkelNFXAmQjFEeNR2CF9eVAhzXe5QUj77kfFCiawj4yOkNHR4HAb9Rmm6HXW371l00-q_7q6UtskAE5w/s1600-h/23+elevated+risk+updated+2.JPG"><img id="BLOGGER_PHOTO_ID_5383740940004900418" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 172px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEigSIpPzsFmgtjAgeO-UXjiR4QhWbqdy8b1TonmDpmsEzfbeM9wAs8YRCbsE0v9TkelNFXAmQjFEeNR2CF9eVAhzXe5QUj77kfFCiawj4yOkNHR4HAb9Rmm6HXW371l00-q_7q6UtskAE5w/s800/23+elevated+risk+updated+2.JPG" border="0" /></a><br /><span style="font-size:85%;">Click Image to Enlarge </span><br /><br /><strong>Last Updated</strong><br /><br />From the graphic above, did you notice that my information on Type I Diabetes has recently changed? The date under Last Updated is July 30, 2009. The report tells me that the update is because “the risks associated with SNPs rs1990760, rs1893217, rs2476601, rs3184504 and rs725613 were updated with newer values. As a result, some customers may find that their results in the Odds Calculator differ slightly from previous values.”<br /><br />When I looked back, my original lifetime scores for Type I Diabetes were Absolute Risk 1.9% (now 1.7%), and Relative Risk 1.91 (now 1.67). I must be living right.<br /><br /><strong>Comparing Type I with Type II</strong><br /><br />As I learned with the other diseases, my risk changes dramatically when I use the Odds Calculator and enter my age range. Although still higher than the average, my risk of developing Type I Diabetes is only 18 out of 10,000. The calculator told me that my biggest risk would have been when I was 10-14 years old.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEis6vdsoZLMFYttUgynVOqimYmL3ot3V-FWt2bJ8qjyRFYxLBStiQmOFB9jI_I4PEtRIpRsXLptsL2OKYGK3WsB2Vkzy8eol22L4XgtIGBPE8gQKqZZP_8REQ_QViH6mJ6jWutlLGCjwwPL/s1600-h/23+Odds+Calculator+Type+I+Diabetes.JPG"><img id="BLOGGER_PHOTO_ID_5383742293839518642" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 215px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEis6vdsoZLMFYttUgynVOqimYmL3ot3V-FWt2bJ8qjyRFYxLBStiQmOFB9jI_I4PEtRIpRsXLptsL2OKYGK3WsB2Vkzy8eol22L4XgtIGBPE8gQKqZZP_8REQ_QViH6mJ6jWutlLGCjwwPL/s800/23+Odds+Calculator+Type+I+Diabetes.JPG" border="0" /></a><br /><span style="font-size:85%;">Click Image to Enlarge</span><br /><br />When I look at my result for Type II Diabetes, I find it under the Typical Risk category. But the odds for me developing Type II are 130 out of 10,000, or more than 7 times that of Type I. Yet Type I is in the Elevated category. My first thought was why would my risks be so different between Type I and Type II?<br /><br />I understand that these risk categories are comparing me to the general population (Relative Risk). But if I ranked the 10 diseases by Absolute Risk, they would fall into different categories I would create, like the Greatest Threat category (which would include Prostate cancer 24%, Type II Diabetes 19%, Venous Thromboembolism 12%), followed by the Moderate Concern category (Psoriasis 9.9%, Age-related macular degeneration 4.3%, Rheumatoid arthritis 2.3%), and finally the Least of My Worries category (Type I Diabetes 1.7%, Crohn’s disease 1.6%, Parkinson’s disease 1.6%, and Celiac disease 0.04%). Of course this ranking could change based on any family history I discover.<br /><br /><strong>More Heritability than the Other Diseases</strong><br /><br />Although the suspected environmental factors for Type I Diabetes are interesting (living in a cold climate, not being breast fed as an infant), out of the ten 23andMe reported diseases, Type I has the highest incidence with 72-88% attributable to genetics.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiQOCpon3vuEi4-zL_gjw56fcZEvbZl8M3GnzmNHF5-j4USWY_AgAZe25srdhDDMEB3bvNwBMLhAVxRPA9taqttJAUYnnCu-zaGiPGzwTFWxMEVu-r4cQV16no8g7dUV5eUAUhw4D9ezG2e/s1600-h/23+Genes+vs+Environment+Type+I+Diabetes.JPG"><img id="BLOGGER_PHOTO_ID_5383743368374728530" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 91px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiQOCpon3vuEi4-zL_gjw56fcZEvbZl8M3GnzmNHF5-j4USWY_AgAZe25srdhDDMEB3bvNwBMLhAVxRPA9taqttJAUYnnCu-zaGiPGzwTFWxMEVu-r4cQV16no8g7dUV5eUAUhw4D9ezG2e/s800/23+Genes+vs+Environment+Type+I+Diabetes.JPG" border="0" /></a><br /><span style="font-size:85%;">Click Image To Enlarge</span><br /><br />In second place is Celiac diseases with 57-87%. Psoriasis with 66-80% came in third. At the bottom is Parkinson’s disease with only 0-1% - which I don’t understand how that could be so low. Type II Diabetes was second to last with 26%, again quite a bit different from Type I.<br /><br /><strong>8 Markers for Type I</strong><br /><br />I find myself looking more closely at the markers reported on for each disease. Crohn’s had 12. Prostate had 5. Type I Diabetes is in the middle of those two with 8. Type II is close with 9. The other reported diseases have only one or two reported markers. Why the broad range in the number of markers? This is another bit of evidence that trying to figure this out is complicated.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjPuuPCfk6He-qalbUlCtGO-CqDlB2LtCyesZlnwi3jEHfh-T0uag2jeIwMEnVLsYRGESpafoJHciEiEMWfrdzr1cFeZMr1d_YwJWFpVsmrzaBOg8r4EHHYfcExgbWjUQ-5j4n0rgjDC-AK/s1600-h/23+Marker+Effects+Type+I+Diabetes.JPG"><img id="BLOGGER_PHOTO_ID_5383744797956615154" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 162px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjPuuPCfk6He-qalbUlCtGO-CqDlB2LtCyesZlnwi3jEHfh-T0uag2jeIwMEnVLsYRGESpafoJHciEiEMWfrdzr1cFeZMr1d_YwJWFpVsmrzaBOg8r4EHHYfcExgbWjUQ-5j4n0rgjDC-AK/s800/23+Marker+Effects+Type+I+Diabetes.JPG" border="0" /></a><br /><span style="font-size:85%;">Click Image To Enlarge</span><br /><br />The SNP reported here in the HLA region had the strongest association with Type 1 Diabetes in one of the largest studies done so far (see the reference below). 23andMe then made an interesting alteration with this note –<br /><br />The <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=PubMed&term=17554300" target="_blank">2007 Wellcome Trust paper </a>reported a strong association between type 1 diabetes and the SNP rs9272346. Our quality control process flagged data for rs9272346 as unreliable, so we instead included the SNP rs3129934, which is also highly associated with type 1 diabetes. Both are in the HLA region, although the exact linkage patterns between tagging SNPs and traditionally determined HLA haplotypes is still being worked out.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjjoXtI8WLa0EO_Zi8TaePqCgk3kpDNrjYTozEBUmCALG95fXRI6VFVtdcaJoGFM8eUud2t-ItYP3T3TkSnGoHo-I39hRLuLO1dJ6z7oTULvPEdf263Xw1xW6VT5AQhB0y_MIa8OSZlEse8/s1600-h/23+Type+I+Diabetes+Technical+Report.JPG"><img id="BLOGGER_PHOTO_ID_5383745879841906626" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 165px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjjoXtI8WLa0EO_Zi8TaePqCgk3kpDNrjYTozEBUmCALG95fXRI6VFVtdcaJoGFM8eUud2t-ItYP3T3TkSnGoHo-I39hRLuLO1dJ6z7oTULvPEdf263Xw1xW6VT5AQhB0y_MIa8OSZlEse8/s800/23+Type+I+Diabetes+Technical+Report.JPG" border="0" /></a><br /><span style="font-size:85%;">Click Image To Enlarge</span><br /><br /><strong>No Family History</strong><br /><br />I can’t think of any 1st, 2nd, or even a 3rd degree relative that has diabetes of any kind. This is good because apparently there is not much one can do try to prevent the onset of Type 1 Diabetes. Here is something I learned from the MD’s Perspective section- a Q&A with Dr. Roshanak Monzavi, M.D., Assistant Professor, Center for Diabetes, Endocrinology and Metabolism, at Children's Hospital of Los Angeles -<br /><br /><strong>23andMe:</strong> Historically, how have doctors used genetics or family history when assessing a person's risk of developing Type 1 Diabetes (T1DM)?<br /><br /><strong>Dr. Monzavi:</strong> Unfortunately, there is currently no proven preventive measure that can be used to decrease the risk of development of T1DM in people with family history of T1DM. However, physicians are studying some interventions that may prevent T1DM or postpone its time of presentation through clinical trials such as <a href="http://www2.diabetestrialnet.org/" target="_blank">TrialNet</a>. Family members of people with T1DM are evaluated for certain genetic and/or immunologic markers, which put them at high risk for T1DM, and if at high risk, they may enroll in such a study to assess the efficacy of an intervention in preventing T1DM.<br /><br />I discovered that a TrialNet study tests whether a daily oral insulin capsule can prevent or delay the disease in at-risk relatives of people with Type 1 Diabetes. TrialNet is also performing a pilot study testing whether docosahexaenoic acid (DHA), and omega-3 fatty acid found in some foods can prevent or delay the autoimmunity leading to type 1 diabetes. Let’s hope they succeed.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg_469ykM_xAw2HHFPI6a7bzDWZkC-sETvWb6zNEXMu_IyKFnlKDzcSX-zcvaaznr-aFqYB38P2jZXdAhgrSuYrkez4yVrDJgdLs_9-yYO11oF1dCcNV8h7WnMMPds2iMS6iUFGlRkAnILF/s1600-h/MarcSWilliams-thumb.jpg"><img id="BLOGGER_PHOTO_ID_5341272521423463202" style="FLOAT: left; MARGIN: 0px 10px 10px 0px; WIDTH: 78px; CURSOR: hand; HEIGHT: 78px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg_469ykM_xAw2HHFPI6a7bzDWZkC-sETvWb6zNEXMu_IyKFnlKDzcSX-zcvaaznr-aFqYB38P2jZXdAhgrSuYrkez4yVrDJgdLs_9-yYO11oF1dCcNV8h7WnMMPds2iMS6iUFGlRkAnILF/s320/MarcSWilliams-thumb.jpg" border="0" /></a><br /><br /><strong>Perspective from a medical geneticist</strong><br /><br /><br /><strong></strong><br /><strong>Communicating Risk</strong><br /><br />One of the real struggles we have in genetics is trying to explain probabilities and risks to our patients. Part of this relates to our brains operating more as pattern recognition engines than analytic computers. The second and more important issue is that there really isn’t a ‘right’ answer to the risk perception question, unless one considers the individual’s perspective. We see this in the prenatal clinical setting all the time.<br /><br />For some couples a slight increase in risk for a certain birth defect (say a 5% risk of having another child with a congenital heart defect) is perceived as so high as to necessitate a battery of testing options, or in some cases choosing not to have more children. In contrast, other couples at a 50% risk for an anomaly will have very few concerns about subsequent pregnancies. Thus we must expand beyond absolute and relative risks to what might be characterized as personal perception of risk.<br /><br /><strong>Aligned With Absolute Risk</strong><br /><br />In his post, Grant developed his own risk categories: Greatest Threat; Moderate Concern; and Least of My Worries. He then categorizes his diseases by absolute risk such that the highest absolute risks are in Greatest Threat (with an apparent absolute risk cutoff of 10%) and the lowest are in the Least of My Worries (with an apparent cutoff of 2%). As with previous posts, Grant has clearly aligned himself with Absolute Risk. He acknowledges that discovery of relevant family history could change the ranking (it appears daily association with geneticists has successfully brainwashed him). But how would it change the assignment? Would Grant still rank this according to an adjusted absolute risk or would family history of disease have a privileged status in ranking risk?<br /><br /><strong>What If the Disease Is Preventable</strong><br /><br />Another potential factor to consider would be the availability of measures to prevent disease. Would this change Grant’s ranking of the diseases? We really can’t tell with the 10 reported diseases because only one of them (type II diabetes) has preventive interventions that seem to work—at least if one extrapolates from studies of hyperglycemic patients without diabetes. For Grant, this is a moot point, as he is at an appropriate weight, eats healthily and exercises. Frankly, based on lifestyle I’m at much higher risk than Grant, although I am also blessed with a completely negative family history of either type I or type II diabetes.<br /><br />So why does this matter? One of the answers has to do with what could be characterized as the utility of the information. In the MD Perspective for both type I and type II diabetes on the 23andme website both physicians acknowledge that there is currently no way to use the genomic predisposition to prevent diabetes. From the medical perspective the testing has no utility, in that the results of the test do not lead to alterations in care that improve the patient’s health outcome. This type of information is frequently used by insurers or health systems to decide whether or not a given test should be covered or even offered to patients.<br /><br /><strong>Personal Utility</strong><br /><br />There is another concept that is beginning to emerge in discussion of genomic testing which is the idea of personal utility. What will this test result mean to me as a person? What will I do if the result is positive or negative? If there is no insurance coverage what am I willing to pay out of my own pocket because I believe this will help me? This principle clearly operates in medicine all the time. The supplement and nutriceutical industry not only survives but thrives as a multi-billion dollar industry almost solely on the basis of personal utility, given that there is limited evidence of increased health benefit (and despite several instances of overt harm. Fen-Phen anyone?)<br /><br /><strong>Folate Flashback</strong><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj2Z4S8fw2ZQFcSWf7tM41kjrMbEz3KUPQZq5MhfGmiBAdY_duY9gt-De4iHr-iO1u2WNB-sjbbJSfI2ebtUzkX3r9quGuzMpMEZb0IkkRvPlzhh-7km-fFENhPrQi9jEeaQkuzaDaKDjDy/s1600-h/folate+bottle.jpg"><img id="BLOGGER_PHOTO_ID_5384113225509827394" style="FLOAT: right; MARGIN: 0px 0px 10px 10px; WIDTH: 133px; CURSOR: hand; HEIGHT: 200px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj2Z4S8fw2ZQFcSWf7tM41kjrMbEz3KUPQZq5MhfGmiBAdY_duY9gt-De4iHr-iO1u2WNB-sjbbJSfI2ebtUzkX3r9quGuzMpMEZb0IkkRvPlzhh-7km-fFENhPrQi9jEeaQkuzaDaKDjDy/s200/folate+bottle.jpg" border="0" /></a><br />I took a daily Folate supplement for a couple of years because I knew: 1) I didn’t eat as many green vegetables as I should; 2) Folate decreases serum homocysteine levels; 3) elevated homocysteine is associated with an increased risk of cardiovascular disease; 4) Even if it doesn’t help, it surely won’t hurt (and it’s easier than eating vegetables!!); 5) It’s cheap. As Folate was systematically studied, it was found that for reasons that still are unexplained, men who had higher Folate intake had more cardiovascular events. Into the trash with my Folate pills!!<br /><br />Bottom line was my decision to spend discretionary income on Folate was based on a belief that Folate supplements would reduce an outcome of concern for me (a heart attack) at an acceptable ‘cost’ (price, lifestyle, added bother to remember to take the pill, etc.). For me, the ‘cost’ of actually losing weight, eating more healthily, exercising regularly, which does have demonstrated utility, is too high. My perception of the personal utility of these health behaviors is too low to justify spending time and effort to achieve them, despite abundance evidence to the contrary.<br /><br /><strong>The Patient Perception Point</strong><br /><br />So what’s the point? (Aha, you assume I have one). From my perspective the issue is that we frequently ignore the disconnect between evidence of utility and a patient’s perception of utility. This leads to recommendations based on sound evidence falling on apparently deaf ears. If we make no attempt to understand what the patient is interested in and why they are interested in it, we may miss opportunities to improve health in ways we don’t anticipate. I now know that Grant is most worried about Prostate Cancer, Type II diabetes and Venous Thromboembolism. Let’s assume that Grant’s health behaviors aren’t as good as they should be. If he were overweight, would his concern about Type II diabetes based on his 23andme results present a teachable moment about what he could do to control his risk?<br /><br />No way to know for sure, but it’s more likely than if his major worry was Crohns disease. I might say, Gee, Grant, you’re really concerned about diabetes and blood clots. Did you know that being overweight really increases your risk for both of those problems? In fact, losing weight has been proven to dramatically reduce your risk of developing diabetes. Is this something you’re ready take on, because if you are, I have a dietician that can help you assess your diet, and I have a list of weight loss programs that will help you to not only lose the weight, but will help you to keep it off.<br /><br />The bottom line for me is listen to the patient, read between the lines, get to the patient’s concern and help them to develop a plan to address the concern. If it takes a 23andme test to get to the concern for that patient, I can live with that—and maybe they can too!<br /><br /><strong>And now for something completely different<br /></strong><br />This is a complete non-sequitur, but as I was playing in Grant’s 23andme site (he lets me log in for the purposes of the blog and I only look at the topic under discussion) I found a tab called timeline. Clicking on this gives a timeline of major discoveries for the disease of interest. In the case of diabetes this goes back to 1550 BC to a citation in the Papyrus Ebers by an Egyptian physician Hesy-Ra describing sweet urine and a variety of dietary cures and ends in 2007 with the Wellcome Trust case control genome-wide association study for type I diabetes. I’m showing my geekitude (geekosity?, geekness?), but I thought it was cool.</div></div>Grant M. Woodhttp://www.blogger.com/profile/18185402177712853914noreply@blogger.com8tag:blogger.com,1999:blog-1887866819730206489.post-57756763111619521782009-09-07T23:45:00.011-06:002009-09-08T00:57:25.936-06:00I Want A New Drug - One That Matches My Genotype<strong>For the readers who are just beginning to follow this blog, please know that the posts of my experience with the 23andMe service are sequential. A list of past blog posts can be found below our pictures on the right. Reading the first post entitled <a href="http://exploringmygenes.blogspot.com/2009/04/influences-on-my-decision.html">What Is This All About</a> is recommended to follow this journey in context.</strong><br /><br /><br /><p><strong>Exploring 23andMe's Pharmacogenomic Information</strong></p>The <a href="http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/">FDA</a> website tells us that “genomic biomarkers can play an important role in identifying responders and non-responders, avoiding toxicity and adjusting the dosage of drugs to optimize their efficacy and safety.” Simply put, <a href="http://ghr.nlm.nih.gov/handbook/genomicresearch/pharmacogenomics">pharmacogenomics</a> is the study of how genes affect a person’s reaction to drugs, and why different people have different side effects.<br /><br />The newly appointed director of the National Institutes of Health, Dr. Francis Collins, said that "pharmacogenomics, which from my perspective has been one of the most promising areas of personalized medicine, has also turned out to be extremely complicated, not that we shouldn't have known that." He also said that a blood-thinning drug called Warfarin “has become a poster child for the future of pharmacogenomics."<br /><br /><strong>Looking at the 23andMe Drug Response Section<br /></strong><br />Warfarin is one of only two drugs (the other being Plavix) that appear under 23andMe’s <em>Drug Response</em> clinical reports section. Another section is called the <em>Research Report</em>. It contains my genetic information on 85 other diseases and traits based on early research that has not qualified yet for the Clinical section. This section lists the only other drug reported on by 23andMe - Statin response. (We’ll look at this section in later posts).<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhWXa68IgsxPbYZ697eH1BPPeQI2YfxN0zDFd2ARgVo_xYhFt5V3Rai-w4bCerO5NpeHLRs8JNqpBF6JMjurLccnrQ5nJSK1YB8b1Z98fFdyb5mpdEYPnHfB_EZiz9vqmN9BE21R3I3TeAb/s1600-h/23+Drug+Response.JPG"><img id="BLOGGER_PHOTO_ID_5378785689641475314" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 191px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhWXa68IgsxPbYZ697eH1BPPeQI2YfxN0zDFd2ARgVo_xYhFt5V3Rai-w4bCerO5NpeHLRs8JNqpBF6JMjurLccnrQ5nJSK1YB8b1Z98fFdyb5mpdEYPnHfB_EZiz9vqmN9BE21R3I3TeAb/s800/23+Drug+Response.JPG" border="0" /></a><br />Click on image to enlarge<br /><br />The report tells me that I have an increased risk for Warfarin sensitivity, which means that if I were ever prescribed Warfarin, my dose should conceivably be slightly less than what is considered typical. The report goes on to tell me that the CYP2C9 and VKORC1 genes are implicated in Warfarin metabolism (which I already know from my work at the Clinical Genetics Institute), and that variants in these genes are consistently associated with Warfarin bleeding complications. A patient’s age, size, other medications, and even diet, are also factored in along with the genotype to compute the most effective dose.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiNeYcc1xsNeoU-IA98gbCfK-6N19a92G70rVZ6eMUjJPoQQ_Y0h8kFfOtz1b_oqUtYEKV5QZX8J-gpJJh-db1b70b0f7g9eFPAJzi-qbW3DLf4CpoQkbKTFfgRjqdNt84QuTAyHNu6mJJR/s1600-h/23+Drug+Response+Warfarin+Genetic+Data.JPG"><img id="BLOGGER_PHOTO_ID_5378786323422318882" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 285px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiNeYcc1xsNeoU-IA98gbCfK-6N19a92G70rVZ6eMUjJPoQQ_Y0h8kFfOtz1b_oqUtYEKV5QZX8J-gpJJh-db1b70b0f7g9eFPAJzi-qbW3DLf4CpoQkbKTFfgRjqdNt84QuTAyHNu6mJJR/s800/23+Drug+Response+Warfarin+Genetic+Data.JPG" border="0" /></a><br />Click on image to enlarge<br /><br /><strong>What I Learned about Warfarin</strong><br /><br />As I read further into the 23andMe report, I learn that two million people take Warfarin. I wasn’t aware that the number is that high. Blood thinners (or anticoagulants) like Warfarin are given to people at high risk for the formation of blood clots due to conditions such as deep vein thrombosis, irregular heartbeat, and heart valve disease or replacement. The drug is also given to prevent recurrence of pulmonary embolism, heart attack and stroke. Patients taking this drug have regular blood tests to evaluate their blood's clotting ability. The doctor uses the results of these tests to adjust the dose up or down accordingly. One difference I noticed between the Drug Response section of my report and the other sections is that there is no MD’s Perspective tab like here like there are for the diseases and carrier status sections.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg2Nk8jm5TFeI-83zLQfmn4qmEcLdlE20Q0-8jIfQci3YJFnl-MMY3WdcTrjAZR_VDDTNXdvw6KRsxGjyzfM0c26h4q-Hz5Hy6zqXv2uLxvPIcgJ17DrQ0UDEx_1aNyoNgEJ6Np1RR1lCNz/s1600-h/23+Drug+Response+About+Warfarin.JPG"><img id="BLOGGER_PHOTO_ID_5378786723122056786" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 309px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg2Nk8jm5TFeI-83zLQfmn4qmEcLdlE20Q0-8jIfQci3YJFnl-MMY3WdcTrjAZR_VDDTNXdvw6KRsxGjyzfM0c26h4q-Hz5Hy6zqXv2uLxvPIcgJ17DrQ0UDEx_1aNyoNgEJ6Np1RR1lCNz/s800/23+Drug+Response+About+Warfarin.JPG" border="0" /></a><br />Click on image to enlarge<br /><br />Pharmacogenomic information is contained in about ten percent of labels for drugs approved by the FDA. A significant increase of labels containing such information has been observed over the last decade. To see a list of drugs currently linked to genetics, see the <a href="http://www.fda.gov/Drugs/ScienceResearch/ResearchAreas/Pharmacogenetics/ucm083378.htm">Table of Valid Genomic Biomarkers in the Context of Approved Drug Labels</a>.<br /><br /><strong>A Few Questions</strong><br /><br />Every genotype variation is either typical sensitivity, or some level of increased sensitivity, which means a decreased dose. Why is it that no genotype requires an INCREASED dose. If it can take weeks of dosing adjustment, what can be the problems or risks a patient might experience during that time? Why would a patient’s age affect a dose?<br /><br /><strong>Don’t Worry Doc – I’m Star One, Star One</strong><br /><br />The report shows my specific genotype (CYP2C9 *1/*1) that is included in any Warfarin dosing algorithm, of which several are being studied. Under the Resources tab, 23andMe has a link to warfarindosing.org. One 23andMe customer who takes Warfarin entered his genotype and other information into this calculator and found it to be very accurate in predicting his optimal dose.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgPYrsAjtMFV0q8T9f2znE5O_A38QU_rZtUrsGS6fxaNYRmDA69inf1RLQF7ClbU5H2LEzHfAjaIOHMHmZyDkj9AkwKQNGbf_3mc5VrfZGJTHoUzLeTHO9s8zQJg8mhD0NjPp65TWDIwdBc/s1600-h/23+Drug+Response+Warfarin+Technical+Report.JPG"><img id="BLOGGER_PHOTO_ID_5378787104250078050" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 205px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgPYrsAjtMFV0q8T9f2znE5O_A38QU_rZtUrsGS6fxaNYRmDA69inf1RLQF7ClbU5H2LEzHfAjaIOHMHmZyDkj9AkwKQNGbf_3mc5VrfZGJTHoUzLeTHO9s8zQJg8mhD0NjPp65TWDIwdBc/s800/23+Drug+Response+Warfarin+Technical+Report.JPG" border="0" /></a><br />Click on image to enlarge<br /><br />The past few years have seen a multitude of <a href="http://intermountainhealthcare.org/hospitals/lds/about/news/Pages/home.aspx?NewsID=105">pharmacogenomic studies</a> with Warfarin dosing. Intermountain Heathcare is participating in a large multi-center, randomized clinical trial with the NIH that will enroll 1,200 participants. Besides the clinical aspects, one other question being asked in some studies is cost effectiveness. Some results show that Warfarin-related genotyping is unlikely to be cost effective for typical patients with atrial fibrillation, but may be cost effective in patients at high risk for hemorrhage.<br /><br /><strong>Final Thoughts</strong><br /><br />Will we have more of this pharmacogenomic info based on or genotype to be informed consumers of medications? Can this work for diet supplements? Will I see any effect from that muscle building shake? And conversely, what fat burning pill will work best for me?<br />Where’s the pharmacogenomic test for brain function and memory enhancement pills? Or Rogaine effectiveness? Or anti-aging therapies?<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg_469ykM_xAw2HHFPI6a7bzDWZkC-sETvWb6zNEXMu_IyKFnlKDzcSX-zcvaaznr-aFqYB38P2jZXdAhgrSuYrkez4yVrDJgdLs_9-yYO11oF1dCcNV8h7WnMMPds2iMS6iUFGlRkAnILF/s1600-h/MarcSWilliams-thumb.jpg"><img id="BLOGGER_PHOTO_ID_5341272521423463202" style="FLOAT: left; MARGIN: 0px 10px 10px 0px; WIDTH: 78px; CURSOR: hand; HEIGHT: 78px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg_469ykM_xAw2HHFPI6a7bzDWZkC-sETvWb6zNEXMu_IyKFnlKDzcSX-zcvaaznr-aFqYB38P2jZXdAhgrSuYrkez4yVrDJgdLs_9-yYO11oF1dCcNV8h7WnMMPds2iMS6iUFGlRkAnILF/s320/MarcSWilliams-thumb.jpg" border="0" /></a><br /><br /><strong>Perspective from a medical geneticist</strong><br /><br /><br /><br /><strong>Warfarin Pharmacogenomics</strong><br /><br />So why did Grant specifically mention Rogaine responsiveness in his last paragraph? It wouldn’t have anything to do with our pictures would it? Look, just because you’re paranoid doesn’t mean they’re not out to get you.<br /><br />Seriously, before I get to the meat of the discussion let me address one question that Grant raised, “Why is it that no genotype requires an INCREASED dose.” In fact there are patients who are resistant to Warfarin and require very high daily doses. A specific alteration in VKORC1, the same gene that Grant carries a change, has been demonstrated to confer extreme resistance to the effects of Warfarin such that patients require 4-5 times the normal dose to achieve a clinical effect. This is a rare enough occurrence that routine testing for this change has not been proposed, although it is suggested that testing be considered if a patient has severe resistance. There are also non-genetic causes of Warfarin resistance (inability to absorb the drug, medications that interfere with Warfarin action).<br /><br /><strong>Putting the WARF in Warfarin<br /></strong><br />Warfarin is one of my favorite drugs because it contains a shout out to my alma mater. The ‘WARF’ in Warfarin stands for Wisconsin Alumni Research Foundation, the organization responsible for commercialization of discoveries at the University of Wisconsin-Madison. GO BADGERS! (we now return you to our regularly scheduled blog). I’ve also had a lot of experience with evaluation of the genetic tests for Warfarin dosing, including co-chairing the workgroup of the American College of Medical Genetics (ACMG) that generated an evidence review and guideline for pharmacogenomic testing for Warfarin.<br /><br /><strong>Tricky Drug to Manage</strong><br /><br />As Grant notes, Warfarin is a very important drug to prevent life-threatening clots in patients with a variety of predispositions. While effective, it is a very tricky drug to manage—too little drug and the patient may clot; too much and they might experience bleeding that can be life-threatening. A number of factors have been identified that affect Warfarin including age, weight, kidney and liver function, other medications and diet. Accounting for all of these factors explains only about 40% of the dose variation from patient to patient. More recently the changes in the genes CYP2C9 and VKORC1 have been shown to explain as much as another 30-40% of the dosing variation. Thus is would seem logical that testing for these genomic variants would be very important to managing this dangerous medication. Certainly the FDA seems to think so.<br /><br /><strong>Introducing ACCE</strong><br /><br />In the words of college football analyst Lee Corso, “Not so fast my friend”. Let’s examine the question more closely. Glenn Palomaki and Jim Haddow developed an evaluation paradigm for genetic tests called ACCE, where ‘A’ stands for analytic validity, ‘C’ stands for clinical validity, ‘C’ stands for clinical utility and ‘E’ stands for Ethical, Legal and Social issues. For this discussion, we’ll not address ‘E’. Analytic validity addresses the question, does the test measure what it is supposed to measure and is the measurement accurate? There are a number of ways to test for the polymorphisms in the two genes of interest, and the evidence shows that they work extremely well confirming analytic validity. So far so good. The next issue is Clinical Validity which asks, is the test result associated with the ‘disorder’ of interest. In this case, the disorder of interest is Warfarin dose. There is abundant evidence that strongly supports the association of genetic variants in these two genes with ability to predict the stable Warfarin dose.<br /><br />Here’s where it gets a bit murky. Based on the robust demonstration of Clinical Validity, many began to actively promote testing in the clinical setting. The argument could be summarized as follows: Given that Warfarin is a dangerous drug if dosed improperly and given that genetic testing has been shown to improve dose prediction, it logically follows that genetic testing to inform Warfarin dose will improve patient safety. On the face of it this seems extremely reasonable however there are numerous examples in medicine that refute the idea that reasonable ideas always improve patient care. What are we missing?<br /><br /><strong>Clinical Utility</strong><br /><br />This brings us to Clinical Utility which simply stated asks, does the result of the test have an impact on patient outcomes of interest? An outcome is a neutral term that encompasses both positive/desirable and negative/undesirable outcomes. In the case of Warfarin, the positive outcome of interest is achieving an appropriate level of anticoagulation for a given patient. The negative outcomes can be associated with not providing enough anticoagulation (undertreatment) leading to clotting, or providing too much anticoagulation (overtreatment) leading to bleeding. From the patient perspective neither is desirable, that is it’s just as bad to die from a clot as from a bleed.<br /><br />Because these severe adverse outcomes are relatively infrequent, it is difficult to study these outcomes directly. Researchers fall back on secondary measures (e.g. time to stable dose, time in therapeutic range) that have some evidence that links them to the clinical outcomes of interest. In the case of Warfarin, there are almost no data that address the issue of clinical utility. The evidence review used by the ACMG workgroup to generate its policy statement identified numerous gaps in evidence such that the workgroup’s conclusion (subsequently endorsed by the ACMG leadership) was that there was insufficient evidence to recommend for or against testing. (Click here for the <a href="http://www.acmg.net/AM/Template.cfm?Section=Policy_Statements&Template=/CM/ContentDisplay.cfm&ContentID=3608">evidence report</a> and <a href="http://www.acmg.net/AM/Template.cfm?Section=Policy_Statements&Template=/CM/ContentDisplay.cfm&ContentID=3633">policy statement</a>).<br /><br /><strong>The Problem of Bleeding</strong><br /><br />Another problem is that virtually all the papers addressing this issue focused on the problem of bleeding. As noted above, this is one of two potential negative outcomes and they are two sides of the same coin. To absurdly illustrate this, let’s assume that we want to eliminate all bleeding events caused by Warfarin? The obvious decision would be to not use Warfarin at all. Sure patients would experience clots, but at least they wouldn’t die of bleeds!! Returning to reasonableness requires the acknowledgement that reducing bleeds could increase the risk of clots. The evidence needs to define the relative balance between these two adverse outcomes in order to decide if a strategy has net benefit or net harm. (This problem is not unique to Warfarin. It is disturbing to me that studies consistently focus only on prevention of adverse events even when there is evidence that this could also reduce effectiveness. Subject for another rant…I mean blog).<br /><br /><strong>Intermountain Healthcare Study<br /></strong><br />To attempt to answer the utility question a prospective randomized clinical trial was conducted at our institution (Intermountain Healthcare) by Dr. Jeff Anderson and his team (reference below). The results of this small trial did not show a net benefit except in certain rare genotypes and interestingly enough in patients with no polymorphisms (so called wild type). It turns out we consistently underdose wild type individuals slightly increasing their risk of clotting. The magnitude of this effect is small, but given that the wild type genotype is the most common, the collective effect may be much larger than anticipated—potentially offsetting the reduction in bleeding events.<br /><br />My group in conjunction with researchers from the University of Washington used this study to examine the cost-effectiveness of testing, the results of which will appear in the journal Pharmacoeconomics in the near future (authors Meckley, Williams, Gudgeon, Anderson and Veenstra). It is interesting to note that none of the references that raise questions about the evidence for testing, or the Anderson study are listed in the 23andME reference list. Why is this? Are they deliberately trying to hide this information? (Excuse me while I adjust my tin foil hat—the black helicopters are back).<br /><br /><strong>The Economic Issue<br /></strong><br />What’s the big deal? If it’s possible that we might be doing good why not test, given that the test cost is fairly cheap (estimated at ~$200 clinically). You may have heard something about the health care crisis we have—it’s been in all the papers (Oh right, we don’t read papers any more. Forget I mentioned it). Let’s do a little math. If we accept that 2 million people are on Warfarin and we assume that they all got the test at $200, then we’ve just cost somebody 400 million dollars! If we get no improvement in medical outcomes (or worse we get poorer outcomes), we’ve injected significant cost into the system with no return in improved health. We can no longer afford to behave like this.<br /><br />Thankfully, others have recognized this issue and there are several large scale prospective studies that are examining genetic testing for Warfarin dosing (include a follow-up study by Dr. Anderson at our institution). Hopefully this means we will know whether or not we should do testing by the time Grant really needs to go on Warfarin!<br /><br /><strong>References<br /></strong><br />McClain MR, Palomaki GE, Piper M, Haddow JE. <a href="http://www.ncbi.nlm.nih.gov/pubmed/18281915">A rapid-ACCE review of CYP2C9 and VKORC1 alleles testing to inform warfarin dosing in adults at elevated risk for thrombotic events to avoid serious bleeding</a>. Genet Med. 2008 Feb;10(2):89-98.<br /><br />Flockhart DA, O'Kane D, Williams MS, Watson MS, Flockhart DA, Gage B, Gandolfi R, King R, Lyon E, Nussbaum R, O'Kane D, Schulman K, Veenstra D, Williams MS, Watson MS; ACMG Working Group on Pharmacogenetic Testing of CYP2C9, VKORC1 Alleles for Warfarin Use. <a href="http://www.ncbi.nlm.nih.gov/pubmed/18281922">Pharmacogenetic testing of CYP2C9 and VKORC1 alleles for warfarin</a>. Genet Med. 2008 Feb;10(2):139-50.<br /><br />Anderson JL, Horne BD, Stevens SM, Grove AS, Barton S, Nicholas ZP, et al. <a href="http://www.ncbi.nlm.nih.gov/pubmed/17989110">Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation</a>. Circulation. 2007 Nov 27;116(22):2563-70.<br /><br />Meckley LM, Gudgeon JM, Anderson JL, Williams MS, Veenstra DL. A Policy Model to Evaluate the Benefits, Risks, and Costs of Warfarin Pharmacogenomic Testing. Pharmacoeconomics in press.Grant M. Woodhttp://www.blogger.com/profile/18185402177712853914noreply@blogger.com6tag:blogger.com,1999:blog-1887866819730206489.post-10181886760449428202009-08-24T06:45:00.007-06:002009-09-08T12:37:39.891-06:00Prostate cancer - Part 2<strong>This is a follow-up from our August 10th post. If you missed it, <a href="http://exploringmygenes.blogspot.com/2009/08/big-pc-what-men-fear-most.html">start here</a>.</strong><br /><br /><strong>Normally Grant writes about a topic from his 23andMe report, followed by commentary from two healthcare providers, Marc Williams and Janet Williams (who happened to be related by marriage - to each other). For this post we reverse the order.</strong><br /><br /><strong><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg5thXQ6wHs_OATtsXM_Xhyphenhyphenit8FJeyt38FXsDHz_the6iWNOU4VqEuprIBIVS03SvFzUtqDZzFtZ1Se7xldRETYFEFgta3NbuhlcqBun3RqfMA6OIUVdzcD_B6HS1i8px5tCLhV3qHv3344/s1600-h/Janet+A+001-1.jpg"><img id="BLOGGER_PHOTO_ID_5363017094122700610" style="FLOAT: left; MARGIN: 0px 10px 10px 0px; WIDTH: 89px; CURSOR: hand; HEIGHT: 100px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg5thXQ6wHs_OATtsXM_Xhyphenhyphenit8FJeyt38FXsDHz_the6iWNOU4VqEuprIBIVS03SvFzUtqDZzFtZ1Se7xldRETYFEFgta3NbuhlcqBun3RqfMA6OIUVdzcD_B6HS1i8px5tCLhV3qHv3344/s200/Janet+A+001-1.jpg" border="0" /></a></strong><br /><br /><strong>Perspective from a Certified Genetic Counselor</strong><br /><br /><br /><br /><br />As someone who works with individuals who are seeking risk assessment for familial cancer, Grant’s result is really frustrating. What in the world does he do with this information?<br /><br />He can remain nonchalant, nonplussed, implacable: “don’t worry, be happy”. He can go to his doctor and discuss this result. The provider may or may not think this information merits consideration in decisions about screening. Should it merit consideration? He can be screened with an exam and a PSA.<br /><br />Grant is now in the position of “waiting” for prostate cancer.<br /><br /><strong>PSA Screening + Genomic data = Prostate Biopsy</strong><br /><br />It doesn’t help that the most publicized story about genomics and prostate cancer (Jerry Gulcher) involves a fellow who is intimately involved with genomic testing. He saved his life by insisting on a prostate biopsy despite a normal PSA. It is difficult to keep any perspective when a story comes out that is so compelling! There is probably much more to his story, but it the short version that gets referenced.<br /><br />The 23andMe result information that Grant now knows may provoke him to seek screening. However, he has no assurances that screening will be anymore sensitive because he is known to have markers found in men with prostate cancer. As recently demonstrated, PSA levels are not consistently sensitive to the presence of prostate cancer. PSA levels can be normal in individuals with advanced prostate cancer. High PSA levels are not caused solely by prostate cancer. Digital rectal exam can reveal nodules or an enlarged prostate, but either can be a benign finding. The presence of the risk markers cannot predict if a high PSA is more likely to be prostate cancer. The markers do not imply reassurance that a normal PSA level rules out prostate cancer. The high-risk markers are not correlated with aggressiveness of prostate cancer or its ability to metastasize.<br /><br /><strong>The Clinical Decision Conundrum</strong><br /><br />The nightmare situation that Grant may not have considered is how this information now shapes the decisions he makes from here on out. For Grant, not acknowledging the risk information would be ironic. He is in the business of incorporating genomic information into medical records and medical care. He believes in the future of genomics and personalized medicine. The current reality is that the evidence to use the information gained in genomic testing does not facilitate the ability to take specific action. In addition, the screening we currently use to detect prostate cancer is itself flawed in its ability to adequately identify men with prostate cancer. We use the test because it is all we have at the current time.<br /><br />Grant is caught between a rock and hard place. He can use his genomic result to direct screening tests with results that are “fuzzy”. The screening tests may indicate risk or suspicion of prostate cancer, but not disease. Prostate cancer can only be diagnosed with biopsy. What is Grant’s threshold for prostate biopsy at this time? How will his provider be able to discuss sound options when there is no evidence to guide a decision (not that that has stopped medicine in the past). I am angry that he now has information that indicates an association with increased risk for cancer, but with no way to apply the information in a way that can prevent or alter the development of prostate cancer. What decisions will Grant make differently because he and his provider now know that he is at increased risk?<br /><br /><strong>Job Security</strong><br /><br />Finally, I am concerned about those who do not have Grant’s laissez-faire attitude about increased risk and cancer. Perception of risk and communicating risk with some perspective is tricky business. I think 23andMe has worked hard to provide ways to visualize and explain the quantity of risk. The complexity of risk and personal reaction to risk - really an “incorporation” of risk into one’s concept of self - is not explored. The upshot is that it may mean job security for me and other genetic counselors.<br /><br /><strong><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiWVPfgUtj9lia4SworfBV8spyu3uO1N2gXptMq_wEFC6JYmJOz7pToCxRQXxZrqCm5Oy9N04KROFPJ0uyTEuJuYSLMA2F2xJEJvWuCnTUp-IJ9fCeJFTiGRR8OJ7EoxL3C423S4ELe3ta5/s1600-h/bioinformatics1.jpg"><img id="BLOGGER_PHOTO_ID_5373413845988458610" style="FLOAT: left; MARGIN: 0px 10px 10px 0px; WIDTH: 126px; CURSOR: hand; HEIGHT: 110px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiWVPfgUtj9lia4SworfBV8spyu3uO1N2gXptMq_wEFC6JYmJOz7pToCxRQXxZrqCm5Oy9N04KROFPJ0uyTEuJuYSLMA2F2xJEJvWuCnTUp-IJ9fCeJFTiGRR8OJ7EoxL3C423S4ELe3ta5/s200/bioinformatics1.jpg" border="0" /></a></strong><br /><br /><strong>Grant's Comments</strong><br /><br /><br /><br /><br />This is great. I’m getting free genetic counseling to help interpret my 23andMe report. Not having a medical professional guide a patient through genetic test results is a common criticism of direct-to-consumer (DTC) testing services. I’m lucky. With Janet, I have that issue covered.<br /><br /><strong>Here Comes My Excuses</strong><br /><br />At this point, I haven’t approached any clinician with my 23andMe information. This includes not talking with a doctor about my prostate cancer risk. Janet has certainly given me a lot to think about. In contemplating my reaction (or lack thereof), I think it comes down to the fact that, from the information I have now (my current and possibly changing genetic risk, my lack of family history, and my age), I don’t have any alarm bells going off in my head.<br /><br />I have learned a lot about PSA screening – and how it is not always useful – both from Janet and from my own research on the Web. One of the arguments against DTC testing is that its clinical utility has not been proven. I find this very ironic in light of a critical point Janet made in her post. “The current reality is that the evidence to use the information gained in genomic testing does not facilitate the ability to take specific action. In addition, the screening we currently use to detect prostate cancer is itself flawed in its ability to adequately identify men with prostate cancer. We use the test because it is all we have at the current time.”<br /><br /><strong>Warning. Editorial comment to follow.</strong> Sometimes the anti-DTC voices do not use the same standard for personal genomics that they do for currently accepted medical practices which also have limited proven utility. In other words, we should not ban DTC testing because of its early stage and many questions concerning its clinical value, just as we will not stop using other sanctioned but vulnerable clinical tests. Interestingly though, results of a survey on awareness of personal genomic testing that I refer to in a following paragraph show some evidence of limited clinical utility. (End of editorial comment.)<br /><br /><strong>A Link Between Prostate and Colorectal Cancer</strong><br /><br />I learned from the 23andMe website that “three SNPs in the same area of the genome have recently been found to be independently associated with prostate cancer risk. This region is called 8q24, because it lies within band 24 on the long arm (named the "q" arm) of chromosome 8. The three SNPs are not close to known genes (although there are others located farther away).” I then discovered this week from the website that both prostate and colorectal cancer have suspected risk-causing SNPs in the 8q24 region. 23andMe tells me about a published study on this subject titled “<a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Search&db=pubmed&term=17618282">A common genetic risk factor for colorectal and prostate cancer</a>.”<br /><br />Although not ready for primetime, 23andMe does include data targeted at my risk for colorectal cancer. This information is listed under their Research Report section in the ‘Elevated Risk’ category. As stated by 23andMe, “Research Reports give you information from research that has not yet gained enough scientific consensus to be included in our Clinical Reports.”<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEikXtBzpyntQvyDVAxnBuCJtCYkaShFWHaDDLd9qzss5uB9lAKzWdkMisI87OBRRcjHyLdiQSyhwtvbb7mF9IGCm90Dz3ASMV_8q03pKIvNVmmk8DjGE1BT3XE_IC-_FpnIojlvmuqWYQaT/s1600-h/Colorectal+cancer+technical+report.jpg"></a><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiasMDsBxCfpMUKcxz3XA_6Tf-pHUPARcvaTRE4u-qU2Bte830YVvWOIhwW5ka3WBbIkMDJ7tk6cgtda0UQs99SvtGrq93wpUbSbDguD9ZoQ-9vACEcz2PvnJxnQh33JxQqQzoj1XeThHam/s1600-h/23+colorectal+cancer+technical+report.JPG"><img id="BLOGGER_PHOTO_ID_5373454515708496738" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 172px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiasMDsBxCfpMUKcxz3XA_6Tf-pHUPARcvaTRE4u-qU2Bte830YVvWOIhwW5ka3WBbIkMDJ7tk6cgtda0UQs99SvtGrq93wpUbSbDguD9ZoQ-9vACEcz2PvnJxnQh33JxQqQzoj1XeThHam/s800/23+colorectal+cancer+technical+report.JPG" border="0" /></a><br />click to enlarge image<br /><br /><strong></strong><strong>The Issue of Risk</strong><br /><br />One of Janet's main concerns with DTC personal genomic services is the communication with and understanding of risk by the consumer. She states that “the complexity of risk and personal reaction to risk - really an “incorporation” of risk into one’s concept of self - is not explored.” An excellent discussion of this topic can be found on the UK’s PHG Foundation website. They have an article titled "<a href="http://www.phgfoundation.org/news/4756/">Understanding DTC genetic risk prediction services</a>" that points out that "because the calculated risk is updated every time a new association is discovered, the prediction for an individual can change from being above average risk to below average risk overnight. This is particularly problematic where it might result in opposing recommendations". The article concludes by saying "companies offering genome-wide risk prediction services should ensure that their customers understand that, whilst the measurement of the DNA sequence itself (the assay) will remain constant, the interpretation of the result (the test) is likely to change as the science develops".<br /><br />Let me quote Janet one last time. She writes "the presence of the risk markers cannot predict if a high PSA is more likely to be prostate cancer. The markers do not imply reassurance that a normal PSA level rules out prostate cancer. The high-risk markers are not correlated with aggressiveness of prostate cancer or its ability to metastasize". I found these three sentences made the most impact on me.<br /><br />Wow. We sure have a lot more research to do.<br /><br /><strong>Awareness of Personal Genomic Tests</strong><br /><br />Also from the PHG Foundation website is an article on a study surveying both <a href="http://www.phgfoundation.org/news/4768/">consumer and healthcare provider knowledge of personal genomics </a>during the year 2008. On the consumer side, of 5,399 respondents, 22% were aware of personal genomic (or direct-to-consumer) tests, 0.3% had used these tests, and two-thirds of these users had shared the test results with a healthcare provider. That would be 2 out of every 1000 patients - certainly not enough for doctors to complain about yet.<br /><br />I found the medical professional survey results really surprising. The 1,880 physician respondents (mostly family physicians, internists, pediatricians, and obstetrician/gynecologists), only 42% were aware of personal genomic tests. Among those aware, 42% had at least one patient who asked questions in the past year about having such a test, and 15% had at least one patient who brought the results of a personal genomic test to them for discussion in the past year. The biggest discovery according to the study was, “among the latter group, which is composed primarily of internists and family physicians, <strong>75% indicated that the personal genomic test results changed some aspect of the patient’s care</strong>, such as screening tests offered, medications or dosages prescribed, lifestyle changes recommended, frequency of follow-up appointments, or diagnoses made.” (Emphasis added of course.)<br /><br /><strong>Getting back to me<br /><br /></strong>Janet is right. It would be a bit embarrassing if I couldn’t make wise decisions related to how I use my 23andMe report since I work in the clinical genomics industry. Should I schedule a prostate cancer screening? The pressure is on.<br /><br /><p><strong>Read the next post - <a href="http://exploringmygenes.blogspot.com/2009/09/i-want-new-drug-one-that-matches-my.html">I Want A New Drug - One That Matches My Genotype</a></strong></p>Grant M. Woodhttp://www.blogger.com/profile/18185402177712853914noreply@blogger.com8tag:blogger.com,1999:blog-1887866819730206489.post-34596738642103540952009-08-10T06:45:00.003-06:002009-09-08T12:34:50.577-06:00The Big PC – What Men Fear MostAlthough my relative risk for <a href="http://en.wikipedia.org/wiki/Prostate_cancer">Prostate Cancer</a> came in third behind <a href="http://en.wikipedia.org/wiki/Crohn%27s_disease">Crohn’s Disease</a> and <a href="http://en.wikipedia.org/wiki/Type_1_diabetes">Type 1 Diabetes</a>, the absolute risk of 24% certainly got my attention. It was the second item I clicked on after looking at Crohn’s. At my age I am supposed to be paying more attention to prostate screening guidelines, but I haven’t been. This risk score may provide a good incentive to do so. Let's read further to see if that’s true.<br /><br />A quick Google search on recent prostate cancer announcements returned several links for radio host <a href="http://www.foxnews.com/story/0,2933,509347,00.html">Don Imus</a> and <a href="http://www.foxnews.com/story/0,2933,509347,00.html">Senator Chris Dodd</a> going public with their diagnoses. This is evidence that this disease is cheerfully bipartisan. At age 48, <a href="http://www.decode.com/">deCODE Genetics</a> co-founder Jeffrey Gulcher reviewed his deCODEme data, which indicated he had a doubled lifetime risk for prostate cancer. Even though his <a href="http://www.cancer.gov/cancertopics/factsheet/Detection/PSA">PSA levels</a> were fairly normal, Gulcher ended up getting a biopsy that revealed a grade 6 (Gleason scale) prostate carcinoma, which was successfully resected. “This test may have saved his life,” deCODE CEO Kari Stefansson said.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiqGU9hlGMKaXFNAJa-0_CuHP8fEdW_dAPTCZVZ4aG-L1DKEPgt7G4iH5xLd_dPj8JTcMKTULrIOvBoPfjQ7TJlSsh6-1H9JieZPptAacDi3d4DBFMznOyvhR-rNC65jyIW9lcNVzGHOHve/s1600-h/23+elevated+risk+updated.JPG"><img id="BLOGGER_PHOTO_ID_5368195391256080194" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 171px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiqGU9hlGMKaXFNAJa-0_CuHP8fEdW_dAPTCZVZ4aG-L1DKEPgt7G4iH5xLd_dPj8JTcMKTULrIOvBoPfjQ7TJlSsh6-1H9JieZPptAacDi3d4DBFMznOyvhR-rNC65jyIW9lcNVzGHOHve/s800/23+elevated+risk+updated.JPG" border="0" /></a><br /><br />As a test for our blog readers - did you notice my risk scores for Crohn’s had been updated since our post on that subject back on July 13th? My absolute risk for Crohn’s increased from 1.5% to 1.6%. The change is because the new score is now gender specific.<br /><br /><strong>Worse Than Death</strong><br /><br />The <a href="http://en.wikipedia.org/wiki/Rectal_examination">digital exam</a> and the threat of <a href="http://en.wikipedia.org/wiki/Erectile_dysfunction">impotence</a> are what men seem to fear more than death from the disease, even though almost 30,000 men die each year from prostate cancer in the United States. More than 185,000 US men develop prostate cancer annually. Among men of all races in the US, prostate cancer is the most common cancer. It is also the leading cause of cancer related death among men of all races.<br /><br />If I develop prostate cancer, I would get to chose from <a href="http://en.wikipedia.org/wiki/Hormonal_therapy_(oncology)">hormonal therapy</a>, <a href="http://en.wikipedia.org/wiki/Brachytherapy">brachytherapy</a>, <a href="http://en.wikipedia.org/wiki/Radical_prostatectomy">radical prostatectomy</a>, <a href="http://en.wikipedia.org/wiki/Cryotherapy">cryotherapy</a>, or just <a href="http://en.wikipedia.org/wiki/Watchful_waiting">watchful waiting</a>. Sounds like a fun treatment menu.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEivy0HB_6GuaGknSr1nIGqRmQBR-rPvIGB6rsvN8JfJ-B57n0aEr8BAFDHo4C2ncV8GHf8nYEBhN3Nd5U7UH6EBIuswgZ3pFKZbZIE3Up1kRoqO0VU5849v13CMGQZ3qE9ESWCu_wKs7YKY/s1600-h/23+Prostate+Cancer.JPG"></a><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhVgpO8u9yFeT-b1LEnMgsN96mOTTyTT-Py46e-AI3oJZjFINRdICWEJs4WoIgBPO2cDJOg3Me7-5bhVlH8j7zRBdK9ZHVY8zsNIx7ZpP3IRMC8N8prW2Ec5vTAU_mfOrPevIxjIk-YVH5B/s1600-h/23+Prostate+Cancer.JPG"><img id="BLOGGER_PHOTO_ID_5368196680134348274" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 284px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhVgpO8u9yFeT-b1LEnMgsN96mOTTyTT-Py46e-AI3oJZjFINRdICWEJs4WoIgBPO2cDJOg3Me7-5bhVlH8j7zRBdK9ZHVY8zsNIx7ZpP3IRMC8N8prW2Ec5vTAU_mfOrPevIxjIk-YVH5B/s800/23+Prostate+Cancer.JPG" border="0" /></a><br /><br /><strong>My Risk and Family History<br /></strong><br />The heritability of prostate cancer is estimated to be 42-57%. This means that genetic and environmental factors contribute nearly equally to differences in risk for this condition. The MD Perspective section made strong references to family history and prostate cancer risk.<br /><br /><strong>23andMe:</strong> <strong>What are the other major risk factors for prostate cancer, besides age?<br /></strong><a href="http://cancer.ucsf.edu/people/shuman_marc.php"><strong>Dr. Marc A. Shuman, M.D.</strong></a> (Professor of Medicine and Urology; Director of the Prostate Cancer Specialized Program of Research Excellence, University of California, San Francisco): Genetics and ethnic background are the main risk factors, other than age, for prostate cancer. A family history of prostate cancer also significantly increases the risk of developing prostate cancer. In addition, African-American men have a significant increase in prostate cancer compared to men of European ancestry. Asian-American men are at a significantly decreased risk of disease.<br /><strong>23andMe: How does heredity influence the risk of prostate cancer?<br />Dr. Shuman:</strong> Family history is one of the most significant risk factors for developing prostate cancer. Men whose first-degree male relatives—fathers or brothers—have had prostate cancer are at increased risk. The risk is doubled in men who have had two first-degree relatives with the disease. Heredity is believed to contribute as much as 40% of the total risk of getting the disease.<br /><br />No grandfathers, father, or uncles have had prostate cancer in my family. Besides my father, I am not aware if they have had any screenings done.<br /><br /><strong>Community Comment 1<br /></strong><br />The <a href="https://www.23andme.com/">23andMe</a> website has a community section that allows for people to post questions and comments. One person said he was surprised by his 23andMe result on prostate cancer. He said –<br /><br />“My father and his two brothers had prostate cancer when they were in their 60's. My older brother had prostate cancer in his mid 40's. I guess this suggests a strong hereditary link. Surprisingly to me, my results say I have slightly lower probability of developing prostate cancer than the average European guy (15.2% versus 17.8%). Maybe there is still a lot to learn about genetic propensity for prostate cancer.”<br /><br />I guess it is possible to have a strong family history, but not have inherited the risk-effecting genetic variants like other family members.<br /><br /><strong>Odds Calculator Shows its Age<br /></strong><br />The default age range in the odds calculator shows that my lifetime risk from 35 to 79 years of age is 24.4 out of 100. This is the absolute risk that appears on my elevated risk screen. However, when I change the range for my current age, the absolute risk reduces significantly to .26 out of 100, that is nearly 100 times less! I also learn as I age every five years, the risk goes up quickly to.95 out of 100,<br />then 2.3 out of 100,<br />then 4.1 out of 100,<br />then 6.2 out of 100,<br />and then 7 out of 100 at 70 years old.<br /><br />This tells me that age by itself is a big risk factor.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiqWUJw7PC6-Jubb4HTY3h3ln3qAI2IjavYScSIUOP8yrI6Hp8DB3JFPhPFqpeGFTPZB9K5xByUwc2TZCkSqWQUtMkFyGLQ8KAzaIgTNvi0NAyI9twxe837o-ugywfMaY4vWfwuArh27-vm/s1600-h/23+Odds+Calculator+Prostate.JPG"></a><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi2WlmMtocBvxz7ydkpYXVWbEIAsn2IAmhx-i76wRSkPD7Kvnkc2ZnQ5uqyeasXl6TZGx8mJFwhxpvdWuiSFYRkF4LG4OCQpI9klJwtbfi8vi7qA8JTdzvp5uDRzOcg2-oDuh5x7QQl3vB9/s1600-h/23+Odds+Calculator+Prostate.JPG"><img id="BLOGGER_PHOTO_ID_5368197881604285298" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 222px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi2WlmMtocBvxz7ydkpYXVWbEIAsn2IAmhx-i76wRSkPD7Kvnkc2ZnQ5uqyeasXl6TZGx8mJFwhxpvdWuiSFYRkF4LG4OCQpI9klJwtbfi8vi7qA8JTdzvp5uDRzOcg2-oDuh5x7QQl3vB9/s800/23+Odds+Calculator+Prostate.JPG" border="0" /></a><br /><br /><strong>My Five Marker Effects (with number six to come later)<br /></strong><br />23andMe analyzes 5 <a href="http://en.wikipedia.org/wiki/Single-nucleotide_polymorphism">SNPs</a> associated with Prostate Cancer: rs1447295, rs6983267, rs10505483, rs1859962, and rs4430796. Based on these markers, estimates of a person's lifetime odds of getting Prostate Cancer can range from 17% to 46%. 23andMe’s estimate is applicable to people of European and African ethnicity, based on available published scientific research (for which the website lists cites of those published studies).<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjF3wjFqY80TuM-BuRAWaXXl7HNnN0GoUmveMK678To_u4GJiHQ3GwO7cHeUThbrj7FbmyscUsVZMtJk_y6oj_UDJsbPIrYdZwk5528CxQC5JHTuc4G5YyHzLId88cr2nVx4lhT0v8PjMsy/s1600-h/23+Marker+Effects+Prostate.JPG"></a><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjOMscLl0-SmVk10G0bxLIoIX-lPUGtirVjiyW2WAHwK9LNf54k8a4-Z0ko1ZvRah371i1_5OtKFikwLXby7K8Tz3Z-VQW8drOJciQuGg00qr4o0lfDUKusgeyZ4iJwf_N-7BESKpLV1_ui/s1600-h/23+Marker+Effects+Prostate.JPG"><img id="BLOGGER_PHOTO_ID_5368198278998283810" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 168px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjOMscLl0-SmVk10G0bxLIoIX-lPUGtirVjiyW2WAHwK9LNf54k8a4-Z0ko1ZvRah371i1_5OtKFikwLXby7K8Tz3Z-VQW8drOJciQuGg00qr4o0lfDUKusgeyZ4iJwf_N-7BESKpLV1_ui/s800/23+Marker+Effects+Prostate.JPG" border="0" /></a><br /><br /><strong>New Paper Points to Another SNP for Prostate Cancer – Then I Point it to Me</strong><br /><br />In the <a href="http://www.pnas.org/content/early/2009/04/21/0902104106.full.pdf+html">Proceedings of the National Academy of Sciences </a>published in April 2009 two recent genome-wide association studies have independently identified a prostate cancer susceptibility locus on chromosome 10q11.2. In summary, they say that if you have the C variant for the SNP rs10993994 (tested in the 23andMe V2-chip), your odds for getting prostate cancer later in life are increased.<br /><br />So I go to the <a href="https://www.23andme.com/you/faqwin/usinggenomeexplorer/">Browse Raw Data</a> section of the 23andMe website and enter in the SNP to see what I have. My 23andMe report allows me to search the more than 500,000 SNPs its microarray chip sequences, even though all of the SNPs may not be currently used in my risk assessment. I find that I have the C variant, which adds 1.47–1.82 to my current cumulative relative risk of 1.37. It will be interesting to track how quickly 23andMe updates my risk estimate.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEidVATMzLc_5fkDYRnqytoKLgR6Qm5haM_SsyUpXIUky5JW_2AjFEHBW5F43OKX3AGXE2pkUEdfI1EtIRyI2dFNVxg6pJQmrL0lxzDCTMcnFiVuOdaa1U2K-s6sXktE3KTQ16ltaWpuj0t7/s1600-h/23+raw+data+prostate+cancer+SNP.JPG"></a><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiJhfAxxilm7tHE_1wfuph3v7pnWaDoRIIjYrDJTs46KJ-fOW5GhExPgL4_6CVKonRRmDKLtRELlRswW1fUx20ckO_zRDTDTTK9uS76gZdARzLRIwlfqptZ376TGwaMaIUZXHbicle6jR0x/s1600-h/23+raw+data+prostate+cancer+SNP.JPG"><img id="BLOGGER_PHOTO_ID_5368198791639130034" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 153px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiJhfAxxilm7tHE_1wfuph3v7pnWaDoRIIjYrDJTs46KJ-fOW5GhExPgL4_6CVKonRRmDKLtRELlRswW1fUx20ckO_zRDTDTTK9uS76gZdARzLRIwlfqptZ376TGwaMaIUZXHbicle6jR0x/s800/23+raw+data+prostate+cancer+SNP.JPG" border="0" /></a><br /><br />Of course, the healthcare IT person in me thinks that this data should be in my EHR (electronic health record), and when a new variant is found to affect risk, this search should be automated and should send a message to me and my healthcare providers. (In fact, <a href="http://intermountainhealthcare.org/genetics">Intermountain Healthcare’s Clinical Genetics Institute</a> is collaborating with the <a href="http://www.hpcgg.org/index.jsp">Partners HealthCare Center for Personalized Genetic Medicine</a> to develop such a solution).<br /><br /><strong>Community Comment 2<br /></strong><br />Another post in the community section asks a question about prostate cancer prevention. A 23andMe representative has answered by sharing a link to the <a href="http://www.mayoclinic.com/health/prostate-cancer-prevention/MC00027">Mayo Clinic website</a> that seems to provide a comprehensive guess. Yet another community post suggests <a href="http://www.thinkgene.com/dehydrated-tomatoes-show-promise-for-preventing-prostate-cancer/">tomato paste</a> may be the secret.<br /><br />With no family history of prostate cancer, a current absolute risk of one-quarter of 1% (which may be updated soon), and a diet heavy on pomegranate juice and tomato paste (OK, maybe not), I’m not sure that I am fully motivated yet to get that first screen done. Who wants to be the first to scold me?<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg5thXQ6wHs_OATtsXM_Xhyphenhyphenit8FJeyt38FXsDHz_the6iWNOU4VqEuprIBIVS03SvFzUtqDZzFtZ1Se7xldRETYFEFgta3NbuhlcqBun3RqfMA6OIUVdzcD_B6HS1i8px5tCLhV3qHv3344/s1600-h/Janet+A+001-1.jpg"><img id="BLOGGER_PHOTO_ID_5363017094122700610" style="FLOAT: left; MARGIN: 0px 10px 10px 0px; WIDTH: 89px; CURSOR: hand; HEIGHT: 100px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg5thXQ6wHs_OATtsXM_Xhyphenhyphenit8FJeyt38FXsDHz_the6iWNOU4VqEuprIBIVS03SvFzUtqDZzFtZ1Se7xldRETYFEFgta3NbuhlcqBun3RqfMA6OIUVdzcD_B6HS1i8px5tCLhV3qHv3344/s200/Janet+A+001-1.jpg" border="0" /></a><br /><strong><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjUC1pRX2YY0sOHY4eYu7Qh-rsRksUQ71kXpKIgMb666WCyj7GSRaygHe-ip7xwDcGTwL-SxD73CbdPo1XEwxh_qvfu1BCmgKEPhskcd00biSmwGvjELsU2vzvYvKREPP2hPF_OeSe8GEce/s1600-h/jwilliams.jpg"></a></strong><br /><strong>Perspective from a Certified Genetic Counselor<br /></strong><br /><br /><br /><strong></strong><br /><strong>Prostate Cancer Serious Business</strong><br /><br />Prostate cancer is the poster boy for men’s health. Sometimes in screening circles you can hear whispers like “breasts get all the money and attention!” No duh. Hmmm. Breasts versus walnut-sized internal organs… So the marketing and money battle may have been lost, but the screening banner should not sag. Prostate cancer is serious business and can be deadly serious.<br /><br />Yet, Grant talks about the screening process as being half the battle in this fate worse than death—the indignity and discomfort of the exam. The 23andMe test result may provide the reason for him to seek screening. (The other tidbit offered up in screening circles: “if men had to do mammography to screen their prostates or other appendages, there would be a better machine.”)<br /><br /><strong>Markers and Prostate Cancer</strong><br /><br />Once Grant read about Crohn’s disease and realized that it didn’t apply to him, he focused on the prostate cancer risk. The 24% risk, as well as the relatively long bars next to the risk percentage, got his attention. He mentions that the risk range offered by the testing is between 17% and 46%. The graph showing Grant’s markers illustrates that three of the five markers were associated with lower risk of prostate cancer. Two markers were associated with increased risk for prostate cancer. Several studies show an association between certain markers and a risk for prostate cancer. The studies do not tell us that the markers cause prostate cancer.<br /><br />Some of the markers are located in places along the genome in which a known gene resides. In a few instances the product of the gene is linked to the prostate. In these circumstances, it makes sense that a change in the gene might affect the prostate. For other markers there is no nearby resident gene and so the biologic role of the marker is unknown. Knowing how and why the markers are associated with the development of cancer might allow for targeted intervention to decrease the risk or prevent prostate cancer.<br /><br />As Grant indicates, new markers and their relative contribution to risk will continue to be found. He looked up a new marker just reported and found that he has it. It will be interesting to see how the additional marker changes his risk. I notice that he didn’t look or didn’t find any markers associated with decreased risk for prostate cancer. None of the markers tell him whether or not he will develop prostate cancer, and if yes, when it will develop or how aggressive it might be.<br /><br /><strong>What’s a Man to Do? Do I Feel Lucky?</strong> <a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiMA2vNuPIb3nRNm4CThhSuQxcqyoedCN5fHsT3eMV0HH1GLnZdzgH0mmiUzdel1mYwZzC-wfNWP3wvmT7_NlEqKBvdWprJ3wY-9u3RDbdqvnVxhQ6YEFte6Wot5QgYGAJ7Xoz4MBNixzCs/s1600-h/DNA+with+human.jpg"><img id="BLOGGER_PHOTO_ID_5368156034669717954" style="FLOAT: right; MARGIN: 0px 0px 10px 10px; WIDTH: 160px; CURSOR: hand; HEIGHT: 320px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiMA2vNuPIb3nRNm4CThhSuQxcqyoedCN5fHsT3eMV0HH1GLnZdzgH0mmiUzdel1mYwZzC-wfNWP3wvmT7_NlEqKBvdWprJ3wY-9u3RDbdqvnVxhQ6YEFte6Wot5QgYGAJ7Xoz4MBNixzCs/s320/DNA+with+human.jpg" border="0" /></a><br /><br />Grant talked about his lack of attention to screening. Unfortunately that is a typical failure in men in Grant’s age group. Technically, Grant isn’t yet of the magic prostate cancer screening age, so he really shouldn’t feel badly. But, because of this result should he start screening now anyway? What should he do? The dread digital? Or perhaps the even more dreaded biopsy?<br /><br /><em>(Just a parenthetical reminder of the recommendation agreed to in testing: Do not use these test results in making management decisions about your healthcare.)</em><br /><br /><strong>Risk Factors Associated with Prostate Cancer</strong><br /><br />The weight of the research so far indicates that family history, ethnicity and age are well known to be associated with determining risk. Having one or more close relatives with prostate cancer (your father, brother, or son) will increase your risk. Being African or African American will increase your risk, being of Asian background reduces the risk. All men have increasing risk as they get older. The fact that Grant does not have a family history of prostate cancer is reassuring.<br /><br />Most studies found the greatest risk in those individuals who had the high risk markers AND family history. Grant’s heritage is white northern European, so higher risk, but not the highest risk ethnicity. Grant is nearing the at risk age group. With the start of screening for prostate cancer should come a discussion about the limitations of the process. However, like it or not, imperfect as it is, it is what we have. At least now there is a reason (perhaps more compelling than age alone) to get the screening done. When to start? Talk to your healthcare provider.<br /><br /><em>Janet is a cancer genetic counselor and has very strong feelings about this which she will share in the subsequent blog post. In a bit of a role-reversal, Grant will react.<br /></em><br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg_469ykM_xAw2HHFPI6a7bzDWZkC-sETvWb6zNEXMu_IyKFnlKDzcSX-zcvaaznr-aFqYB38P2jZXdAhgrSuYrkez4yVrDJgdLs_9-yYO11oF1dCcNV8h7WnMMPds2iMS6iUFGlRkAnILF/s1600-h/MarcSWilliams-thumb.jpg"><img id="BLOGGER_PHOTO_ID_5341272521423463202" style="FLOAT: left; MARGIN: 0px 10px 10px 0px; WIDTH: 78px; CURSOR: hand; HEIGHT: 78px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg_469ykM_xAw2HHFPI6a7bzDWZkC-sETvWb6zNEXMu_IyKFnlKDzcSX-zcvaaznr-aFqYB38P2jZXdAhgrSuYrkez4yVrDJgdLs_9-yYO11oF1dCcNV8h7WnMMPds2iMS6iUFGlRkAnILF/s320/MarcSWilliams-thumb.jpg" border="0" /></a><br /><br /><strong>Perspective from a medical geneticist</strong><br /><br /><br /><strong></strong><br /><strong>An Alternative View</strong><br /><br />Jeffrey Gulcher Chief Scientific Officer of deCODE genetics (a company that offers a direct-to-consumer genomic test service called deCODEme) had a less ambivalent response than Grant to his increased risk of prostate cancer. He opted to visit his physician and had a blood test to measure his prostate-specific antigen (PSA). The test was normal, albeit in the high end of the normal range. Despite the normal result he pursued a prostate biopsy which <a href="http://www.geneticsandsociety.org/article.php?id=4189">revealed the presence of aggressive prostate cancer</a> that fortunately had not metastasized.<br /><br />Still, several questions are raised: How should a PSA test be interpreted if one has increased risk based on genotyping? (Answer we don't know.) How should a PSA test be interpreted based on the presence or absence of a family history of prostate cancer? (Answer we don't know.) Does evidence support population screening with PSA? (Answer - not according to either the <a href="http://www.ahrq.gov/CLINIC/USPSTF/uspsprca.htm">United States Preventive Services Task Force</a> and the <a href="http://www.acpm.org/pcscreening.htm">American College of Preventive Medicine</a> both of which in 2008 concluded that there is insufficient evidence to recommend routine population screening with PSA.)<br /><br />While not denying the likelihood that these choices were likely life saving for Dr. Gulcher, if a large number of men pursued this course of action what benefits and harms would they experience? Would the situation be analogous to <a href="http://en.wikipedia.org/wiki/Full-body_scan">full-body CT scanning</a> where 9 out of the 10 findings are incidental and have no health impact? Pursuit of these "<a href="http://en.wikipedia.org/wiki/Incidentaloma">incidentalomas</a>" consumes scarce health care resources and, in some cases, leads to invasive procedures with attendant morbidity and occasionally mortality. I would find counseling a patient presenting to me with a test result extremely challenging.<br /><br /><p><strong>Read the next post - <a href="http://exploringmygenes.blogspot.com/2009/08/prostate-cancer-part-2.html">Prostate cancer - Part 2</a></strong><p>Grant M. Woodhttp://www.blogger.com/profile/18185402177712853914noreply@blogger.com2tag:blogger.com,1999:blog-1887866819730206489.post-20326305693117202352009-07-27T11:30:00.006-06:002009-09-08T12:31:59.589-06:00Carrier Status – Do you have your tracking number?Before we review my two other elevated disease risks items (see last post), let’s take a first look at one of the other categories in the clinical report – Carrier Status. The report includes possible variants for eight diseases. I am only a carrier for one; Hemochromatosis. I did click that one first to find out what it was, but I will address that in a later post. Because my work involves supporting programs around expanded newborn screening, I will start with Cystic Fibrosis (CF), which is one of the tests included in the screening.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEihknHfofAEIZEv1p98729sXrnwz16FwodBlJ5oWqgq_PeR3DU42w4pcA3sl-VzTJmE_EnJHPRzADPvfpn3gKjVBmUKz3atPw4LozqLN-nccTkjBvxx0fyO-CZfECkBb6Fse_NVxYPBNMco/s1600-h/23+carrier+status+2.jpg"><img id="BLOGGER_PHOTO_ID_5363159598239043426" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 283px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEihknHfofAEIZEv1p98729sXrnwz16FwodBlJ5oWqgq_PeR3DU42w4pcA3sl-VzTJmE_EnJHPRzADPvfpn3gKjVBmUKz3atPw4LozqLN-nccTkjBvxx0fyO-CZfECkBb6Fse_NVxYPBNMco/s800/23+carrier+status+2.jpg" border="0" /></a><br /><br /><strong>About the DeltaF508 Mutation</strong><br /><br />Clicking on the link for more information about the disease, I learned that one in every 3,000 babies born to parents of European ancestry in the U.S. has CF, making it the second most common inherited disorder. It was also interesting to learn that the incidence is lower in African-Americans (1 in 15,000) and Asian-Americans (1 in 30,000).<br /><br />For newborn screening, a majority of states recommend that all babies be screened for CF at birth by analysis of blood (one or two drops from a heel stick). Depending on the particular state's program, in many instances this screening includes mutation analysis of the CFTR gene. My first question is do we store the result in the baby’s electronic health record? If not, should it be? And why is it that this mutation doesn’t eventually die out?<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEivyaRR8JS0Z5YOSk5M76AXgknzzwSxLCuF-LlrZf1BDB6AQqHCh9x3zPZ3hia_6Qd6HI3Z9nT4wTYilAp6rBbLGniU0APWpUU3yI8xRYR8DoJYhP87k0-9rWMTPbC_gQgRmgchqHZFgJcZ/s1600-h/23+cystic+fibrosis+2.JPG"><img id="BLOGGER_PHOTO_ID_5363163073698821698" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 206px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEivyaRR8JS0Z5YOSk5M76AXgknzzwSxLCuF-LlrZf1BDB6AQqHCh9x3zPZ3hia_6Qd6HI3Z9nT4wTYilAp6rBbLGniU0APWpUU3yI8xRYR8DoJYhP87k0-9rWMTPbC_gQgRmgchqHZFgJcZ/s800/23+cystic+fibrosis+2.JPG" border="0" /></a><br /><br /><strong>The MD Perspective section</strong><br /><br /><p>Here are three clinical facts and guidelines I learned from the MD Perspective section -</p><p>1. Being aware of a family history of CF should lead to genetic counseling for couples considering a pregnancy in which the inheritance of CF as well as its range of clinical manifestations is discussed.<br />2. There are more than 1,500 known mutations in the CF gene, but about 25-30 of these mutations account for 90% of the mutations found in people with CF.<br />3. It is important to determine the specific CF mutations in all patients with CF, since drugs specific for treatment of particular CF mutations are being developed, making it imperative that clinical researchers know the specific CF gene mutations present in their patients with CF (known as their "CF genotype").<br /><br /><strong>Salty kids in the Middle Ages</strong><br /><br />The Timeline tab listed 11 dates from the Middle Ages to 1993 with historical milestones around the understanding of CF. I enjoyed the first entry -<br /><br />People in the Middle Ages have a saying that modern-day scholars take as a <a href="http://books.google.com/books?id=i9lXQ6xb-HsC&pg=PA14&lpg=PA14&dq=woe+to+that+child+which+when+kissed+on+the+forehead+tastes+salty+he+is+bewitched+and+soon+must+die&source=web&ots=EvhO-wqrR3&sig=Bn0kBXm9z_jnn_tAF66-otbbPEE">reference to cystic fibrosis</a>: "Woe to that child which when kissed on the forehead tastes salty. He is bewitched and soon must die." Centuries before the gene that is mutated in cystic fibrosis would be found, people saw excessively salty sweat as a premonition of sickness, emaciation, and early death.<br /><br /><strong>Genetic Counseling and other Resources</strong><br /><br />Another genetic testing company called Navigenics includes an hour of genetic counseling in the price of their service. 23andMe does not, but under the Resources tab, one finds a link to the National Society of Genetic Counselors to help you locate a counselor in your area.</p><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhUor_wYNzbmKiDmjMtLj9mX9UGo5o9grf3t-n0ZoFlRxqgh8TUmIak6XInrmdYl9ls8EPGVMa3YbFl9-e7VUypEPSgmz0ljCIj0N-S09MEVrBGy8nzCgaXPMDt1IZTg1_tYxzOj8YSVDpL/s1600-h/23+cystic+fibrosis+resources.JPG"><img id="BLOGGER_PHOTO_ID_5363164483464324354" style="WIDTH: 440px; CURSOR: hand; HEIGHT: 362px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhUor_wYNzbmKiDmjMtLj9mX9UGo5o9grf3t-n0ZoFlRxqgh8TUmIak6XInrmdYl9ls8EPGVMa3YbFl9-e7VUypEPSgmz0ljCIj0N-S09MEVrBGy8nzCgaXPMDt1IZTg1_tYxzOj8YSVDpL/s800/23+cystic+fibrosis+resources.JPG" border="0" /></a><br /><br /><strong>Showing My Results to the Public</strong><br /><br />Back on July 13th we premiered the first of my actual results on this blog. Four days later I was in Denver presenting to over one hundred people attending a conference by the <a href="http://mostgene.org/2009_Meeting_Agenda.html">Mountain States Genetics Foundation</a>. Speaking in the 'Experimental Man' slot of the agenda (with an emphasis on ‘mental’), I logged in to my 23andMe report and projected it for all to see. Many in the audience were skeptical of direct-to-consumer genetic testing services. The goal of my presentation was not to change opinions, but rather to have a dialogue on the issue based on a better understanding on what the services are about.<br /><br />No matter the point of view, I think all found the content of the 23andMe report very interesting. It led to a fun discussion related to whether or not one would want to know this kind of information about themselves. Would our desire be different depending on the disease? Is the report reliable and accurate healthcare education or just entertainment? How might having this information effect patient questions during visits with doctors and genetic counselors?<br /><br /><strong>More Than My Result</strong><br /><br />Beyond my carrier status for CF, however, is a recent news article about a possible new treatment that is claimed to be the most efficient gene <a class="kLink" oncontextmenu="return false;" id="KonaLink0" onmouseover="adlinkMouseOver(event,this,0);" style="POSITION: static; TEXT-DECORATION: underline! important" onclick="adlinkMouseClick(event,this,0);" onmouseout="adlinkMouseOut(event,this,0);" href="http://www.upi.com/Science_News/2009/07/21/Cold-virus-used-in-cystic-fibrosis-study/UPI-19801248196759/#" target="_new">therapy</a> for cystic fibrosis to be found in the last 20 years. The therapy uses a common cold virus to deliver a corrected gene to cystic fibrosis cells that restores normal function to lung tissue. This type of research is exciting to follow.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg5thXQ6wHs_OATtsXM_Xhyphenhyphenit8FJeyt38FXsDHz_the6iWNOU4VqEuprIBIVS03SvFzUtqDZzFtZ1Se7xldRETYFEFgta3NbuhlcqBun3RqfMA6OIUVdzcD_B6HS1i8px5tCLhV3qHv3344/s1600-h/Janet+A+001-1.jpg"><img id="BLOGGER_PHOTO_ID_5363017094122700610" style="FLOAT: left; MARGIN: 0px 10px 10px 0px; WIDTH: 89px; CURSOR: hand; HEIGHT: 100px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg5thXQ6wHs_OATtsXM_Xhyphenhyphenit8FJeyt38FXsDHz_the6iWNOU4VqEuprIBIVS03SvFzUtqDZzFtZ1Se7xldRETYFEFgta3NbuhlcqBun3RqfMA6OIUVdzcD_B6HS1i8px5tCLhV3qHv3344/s200/Janet+A+001-1.jpg" border="0" /></a><br /><strong><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjUC1pRX2YY0sOHY4eYu7Qh-rsRksUQ71kXpKIgMb666WCyj7GSRaygHe-ip7xwDcGTwL-SxD73CbdPo1XEwxh_qvfu1BCmgKEPhskcd00biSmwGvjELsU2vzvYvKREPP2hPF_OeSe8GEce/s1600-h/jwilliams.jpg"></a></strong><br /><strong>Perspective from a Certified Genetic Counselor</strong><br /><br /><br /><br /><br /><strong>Introducing Janet Williams</strong><br /><br />This is the first opportunity that I’ve had to respond to Grant regarding the information he has been provided as part of genomic testing through 23andMe. It is probably not surprising that like Marc, I also expressed skepticism when I first learned about the premise of 23andMe and again when Grant indicated that he went ahead and sent in a sample for analysis. All sorts of counseling nightmares ran through my mind—and all that before I really had any idea about what would be tested or how test results could be communicated. Incredulity did not adequately express my response. I have spent 30 years in the fine art of genetic counseling and this company planned to offer genomic test results regarding the entire genome without meeting or talking with individuals!<br /><br /><strong>Counseling the Report</strong><br /><br />My first introduction to 23andMe and its representatives came at an annual meeting of the National Society of Genetic Counselors (NSGC). A glimpse of the sample result report was offered and feedback invited. The example report included the Cystic Fibrosis (CF) carrier screening result. I was quite dismayed by what I read. I gave the company representative an earful and I wasn’t the only genetic counselor who did! In that original version of the carrier report, the interpretation unequivocally stated that the tested individual was not a carrier for CF, rather than that the individual is not a carrier for the DeltaF508 mutation. Several weeks after that meeting, when I learned that Grant had done testing, I nervously asked him about his CF result. I was “primed” to tell him what the CF carrier result really meant and why it incorrectly portrayed carrier testing results.<img id="BLOGGER_PHOTO_ID_5363166142442829970" style="FLOAT: right; MARGIN: 0px 0px 10px 10px; WIDTH: 213px; CURSOR: hand; HEIGHT: 320px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg-XNotVdjPQZbHKpLWgEHPJyQ_Z8wkBIt5Axb4XPmFlUfnTpQLGxNNUFB4qplTvGiSyJfCajNPWfECxAr0gx8Scz2Dlt0542TKQdDgxI98enjKIYSw68oW5VztiyzSNRPRi85PhSfBRVnW/s320/genetic+counseling1.jpg" border="0" /><br /><br />Fortunately, Grant is not a carrier for the DeltaF508 mutation. I was very pleased to find that the wording of the interpretation of the result had changed and that the wording is now much more appropriate for the information disclosed by testing. The results page for Grant now indicates that individuals who are seeking information about carrier status to assess family risk for CF need to use the recommended panel for more complete carrier detection.<br /><br /><strong>Disease Risk Different from Carrier</strong><br /><br />Overall, the carrier status section is based on testing for known changes in specific genes well characterized to be associated with a specific disease, e.g. the HFE gene and hemochromatosis (a result of higher interest for Grant), BRCA1/2 and hereditary breast and ovarian cancer. For this blog, the specific change we are talking about in this entry is the DeltaF508 mutation in the specific gene known as the cystic fibrosis transmembrane conductance regulator (CFTR) that when present in two copies is associated with the specific disease CF. In the previous discussion of Crohns disease, the emphasis was on SNPs and haplotypes and the risk for disease. In carrier testing for CF the emphasis is on a specific DNA finding.<br /><br />The DeltaF508 mutation is a specific DNA change in the CFTR gene that results in a non-functioning product (protein) of the gene. Having one gene mutation in the CFTR gene does not result in CF. So a question might be, “why do we even test for a CFTR mutation?” The emphasis for DeltaF508 testing is more about the risk to pass on that specific DNA finding, rather than the risk to develop disease. This is not the case with each of the conditions lumped under the “carrier status” section of the 23andMe report. In the blog, we plan to go through each of the conditions listed on Grant’s report and to discuss the meaning of each test result in relation to being a “carrier”.<br /><br /><strong>Why Carrier Screening for Cystic Fibrosis</strong><br /><br />Because of the severity of CF, carrier screening is recommended by several professional associations including the American College of Obstetrics and Gynecology, the American College of Medical Genetics, the American Academy of Pediatrics and the American Academy of Family Practice. Recommended screening for CF mutation carriers in people of European Caucasian background consists of a panel of 25 – 30 gene mutations in the CFTR gene, of which DeltaF508 is just one. It is the most common mutation, but just knowing the DeltaF508 carrier status is not truly carrier screening for family risk planning.<br /><br /><strong>Need More Information on What It Means to be a Carrier</strong><br /><br />The accompanying information about CF provided by 23andME gives a good description about what to expect if you have CF. [That is you are found to have two copies of non-functioning CFTR genes; one of which is often a DeltaF508 gene mutation, but the other could be any of more than 1500 gene mutations.] The information regarding carrier status for CF is fairly spartan. The focus on the disease symptoms of cystic fibrosis is somewhat misplaced. The more common test result will detect carriers and so concentrating information about the disease may not provide the best service.<br /><br />While test results will detect an individual with two DeltaF508 mutations, the likelihood of someone getting this test (after age 18) and not knowing that they have CF due to the presence of two DeltaF508 mutations is extremely low. Classical CF leads to significant illness with severe symptoms. It is also possible to have a milder form of CF and have one DeltaF508 mutation and another mutation that leads to less severe illness, more often referred to as non-classical or atypical CF. The result most people are likely to have is variant present, i.e. a “carrier” or variant absent, i.e. a “non-carrier”.<br /><br /><strong>Grant's Reaction</strong><br /><br />In reading Grant’s post, he didn’t really indicate anything about how he felt about being found a “non-carrier” of the DeltaF508 gene mutation. It probably didn’t mean much at all. Grant is a really curious guy and has investigated many aspects of his report, but it may be that those conditions that are low risk or non-risk are just not all that engrossing. Why would Grant pay much attention to the fact that this is just another of the non-carrier conditions? When might one pay closer attention to the presence or absence of any given variant? What would either variant result mean to someone who is planning a pregnancy in the near future? Should you use this test result to seek medical information?<br /><br />The results section has the opportunity to delve much more deeply into implications of being a carrier of a DeltaF508 mutation. It is a topic covered richly in the published literature because of newborn screening for CF as well as the professional recommendations for carrier screening. Since Grant is not a carrier, that discussion will have to wait for a genetic counseling session.<br /><br /><strong>Screening for the Counselors</strong><br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhLfn5NArGO5-_R5HHxQYnQ0w3CKOnyBi4rzyFrCZ7q14GTEEY4iMcchhU6_IPNTFczh5-Ke276_k8iipq5b_wz0Y25NGY0AlZq6lzs5Hp9Pwh-sphrswtU8OeADYR75lssFimUImgW0gQR/s1600-h/bioinformatics5.jpg"><img id="BLOGGER_PHOTO_ID_5363171828597349570" style="FLOAT: left; MARGIN: 0px 10px 10px 0px; WIDTH: 182px; CURSOR: hand; HEIGHT: 320px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhLfn5NArGO5-_R5HHxQYnQ0w3CKOnyBi4rzyFrCZ7q14GTEEY4iMcchhU6_IPNTFczh5-Ke276_k8iipq5b_wz0Y25NGY0AlZq6lzs5Hp9Pwh-sphrswtU8OeADYR75lssFimUImgW0gQR/s320/bioinformatics5.jpg" border="0" /></a>I am not naïve to the option about DeltaF508 mutation screening. Sometime in the early 1990s, again at an NSGC meeting, a vendor booth offered the opportunity for genetic counselors to give a sample as a part of a trial of the commercial offer to do testing for CF. At the time, the test was new and no other mutations had been reported in the CFTR gene. Genetic counselors were given the opportunity to be guinea pigs in the test analysis. I don’t recall elaborate pre-test information (though there might have been) and although I didn’t expect to know results, a letter came with my result.<br /><br />As my photo reveals, I am of the European Caucasian variety of people. It is possible, though there is no family history of CF, that I could carry the CF DeltaF508 mutation—almost 1 in 30 people like me do. I was relieved to know that I do not carry the mutation and I have not forgotten that I do not carry the mutation. I imagine that if I had been found to carry it, that I would be talking with my daughters about CF carrier probabilities and screening options. I don’t carry it, but I am still talking with my adult daughters about CF carrier screening.<br /><br /><strong>When to Talk with Your Healthcare Provider</strong><br /><br />So if you have a DeltaF508 mutation what does it mean? Should you talk with your health care provider about knowing this? When? I do think it is relevant to discuss this result with your provider, especially if you are planning on having children in the future. The best time to address risk for CF is prior to pregnancy—prior to conception! It does take two to have risk for a baby to have CF and so your testing and your partner’s testing can and should occur prior to pregnancy. This allows for full conversation regarding options and choices around risk for CF. The single mutation test offered through 23andMe is not adequate for these types of discussions. The admonition not to use the results to make medical decisions is good advice. The appropriate testing for carrier status for CF is best determined by a conversation with your OB/GYN or better yet with a genetic counselor.<br /><br /><strong>Final Thought</strong><br /><br />Grant raised the question, “Why is it that this mutation doesn’t eventually die out?” That is a very interesting discussion about evolutionary concepts involving selective advantage and genetic drift and founder effect. Suffice it to say, we don’t know yet with CF, but when Sickle Anemia carrier status is discussed, we can put forward a little about these population concepts. I’m hoping that is Marc’s topic!!<p><strong>Read the next post - <a href="http://exploringmygenes.blogspot.com/2009/08/big-pc-what-men-fear-most.html">The Big PC – What Men Fear Most</a></strong></p>Grant M. Woodhttp://www.blogger.com/profile/18185402177712853914noreply@blogger.com3tag:blogger.com,1999:blog-1887866819730206489.post-23620119683334163142009-07-13T07:15:00.009-06:002009-09-08T12:20:21.001-06:00The Grand Opening - Looking Inside My Genetic Crystal BallWhen I tell people that I completed a 23andMe test, they all seem to have the same reaction. The question they ask is – so when are you going to die, and of what disease?<br /><br />I am supposed to know enough about interpreting genetic information to prevent me from responding the same way. However, I have to admit that deep down the same emotionally-based thoughts did exist. Because of our imminent mortality, it is natural for us to ask whether we will learn something about our futures from these types of tests.<br /><br />After sending in the spit tube and waiting a couple of weeks, I received an email announcing that my results were ready. I was instructed to login at the 23andMe website to an account I had previously created when I ordered the test kit. Once logged onto the site, I found a welcome screen that was filled with links for announcements, new articles, new surveys, and recent community posts. A long main menu block was displayed on the left side of the page, and at the top of the menu was a category titled “health and traits”. The first selection under this category was Clinical Reports. Clicking here would finally open the “secret vault” containing my genetic information.<br /><br /><div><strong>My Elevated Risk</strong><br /><br />The initial screen presented after clicking Clinical Reports divided the report into four sections - disease risks, carrier status, traits, and drug response. Under Disease Risks I saw a sub-list of five diseases, but I quickly clicked the link that said see all 10 risk reports … Another screen appeared with 23andMe’s list of these ten diseases divided into three risk levels – Elevated Risk, Decreased Risk, and Typical Risk. (For this post, I am sharing only the Elevated Risk section. Various parts of the complete report will be shown over multiple posts.<br /><br /><img id="BLOGGER_PHOTO_ID_5357938332681620130" style="DISPLAY: block; MARGIN: 0px auto 10px; WIDTH: 440px; CURSOR: hand; HEIGHT: 173px; TEXT-ALIGN: center" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgdvhdR5tfOiTtf6UZnKJGKDmo3iAtP4IUzkyFVCfOWKkCgmpKbouuN-Po2i2Wr4laOm17X4pDrSA7rYd21fbKZBBtAPdNSVD0Uov5f-UoJNpTlavkCuDsWCz6G0Z-iFbnDVbRg9CHtn5Qy/s800/23+elevated+risk-2.jpg" border="0" /><br /><strong>Crohn’s disease risk is 3 times!</strong><br /><br />Wow. So for me Crohn’s disease was the big winner. Interesting. Not something I would have guessed. At first glance, a 300% percent increased risk sounded serious, but then I saw the absolute risk was only 1.5%. Whew. (It dropped even further when I used the odds calculator for my age. See below.) But wait. Should I be more worried that my absolute risk for Prostate cancer was 24%? We’ll come back to that one later. Until then - the question I needed to answer first - what is Crohn’s disease anyway? I’d heard of it, but I needed to learn more. When I clicked on the Crohn’s Disease link I got the following screen.<br /><br /><img id="BLOGGER_PHOTO_ID_5357940304306993570" style="DISPLAY: block; MARGIN: 0px auto 10px; WIDTH: 440px; CURSOR: hand; HEIGHT: 267px; TEXT-ALIGN: center" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEivR7qSU6fs7p1z68hnElZXH2P3baCnnOwqSthTidZRRwMJYkD1U0bb4jRM8v4CmPYtdS_dKZesBl6zzXOZ6JAbNqlUtkl3ir3kD5gmnFoMYOr2N5jSVf7xx1YuS88GZOENPxS4IaWdsSqZ/s800/23+Crohn%27s+Disease-1.JPG" border="0" /><br />This screen contained a nice summary explaining Crohn’s disease. I also followed links to even more detailed information on the disease. After feeling that I had acquired a lot of knowledge around Crohn’s, I scrolled further down the same page and found the Odds Calculator.<br /><br /><img id="BLOGGER_PHOTO_ID_5357941238722953634" style="DISPLAY: block; MARGIN: 0px auto 10px; WIDTH: 440px; CURSOR: hand; HEIGHT: 223px; TEXT-ALIGN: center" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhp3rhBKiaLDjlm-uxoBWCJ_IJwJIKIictnY_kCBvbK-xmqT-VOrqKttbCV1nVQKb3u0q1Wp_0IljbNdeTuroqyWSJoCDTRfvT0VHUisPaVr1QP0n7dBd_QJXxwxkbgfDLNjVsZgrAuX8yK/s800/23+Odds+Calculator-1.JPG" border="0" /><br />When I selected my ethnicity and age range, the odds changed. The absolute risk numbers went down significantly from 1.5 out of 100 to only 0.18 out of 100. The relative risk also dropped from 0.49 out of 100 to only 0.06 out of 100. As I played with the calculator, I learned that the odds increased as I got older.<br /><br /><strong>What? It’s not just Genetics?</strong><br /><br />Next I learned that along with genetics, environmental factors play a big role in the development of disease. In other words, genetics is not the only cause of disease. I know that most people do not know about <a href="http://en.wikipedia.org/wiki/Genetic_epidemiology">genetic epidemiology</a>, which is the study of the role of genetic factors in determining health and disease in families and in populations, and the interplay of such genetic factors with environmental factors. So this bit of information is very important.<br /><br /><img id="BLOGGER_PHOTO_ID_5357941757982187458" style="DISPLAY: block; MARGIN: 0px auto 10px; WIDTH: 440px; CURSOR: hand; HEIGHT: 92px; TEXT-ALIGN: center" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgK4D3gH9Az4h67mHa9j0GbrR1GL6gTeWIesRO1z3aIkQTHRyy702P0bbLo7GwODm37x6ScDBp_WbyJvwhip8tFPzDjwcBDslGibPlV_NnHZxFpT1PQtnKHi7zrPn0eQ4Z5l1TCrIbCHRGw/s800/23+Genes+vs+Environment-1.JPG" border="0" /><br />If only half of the cases of Crohn’s can be attributed to genetics, then half get the disease for reasons other than genetics! I learned that this is true for the other diseases as well – just with different percentages.<br /><br /><strong>What does my Family Health History Tell Me?</strong><br /><br />I have learned from the time I have been working with the Clinical Genetics Institute that my family health history can also help me understand my genetic risk. The only family history of Crohn’s disease I am aware of is a cousin who developed Crohn’s after getting liver disease. I should look into this further and talk with more realtives.<br /><br />As I add all of this information together, I decided that worrying about Crohn’s disease was not necessary. I also realized that I didn’t need to run out right away and alert my doctor. But maybe - if sometime in the future I develop symptoms like diarrhea, cramping, or bleeding, and a diagnosis is slow in coming - I can mention to the doctor to look at the possibility of Crohn’s – based on this “new” discovery of my genetic risk. Since 23andMe told me that the clinically-relevant genetic knowledge on this disease and others is changing, I will come back to my report later to see what - if anything - has been updated.<br /><br /><strong>More to Come</strong><br /><br />As you can see in the screenshot, the page with the summary on Crohn’s disease contains other tabs called ‘How it Works’, ‘Timeline’, ‘MDs Perspective’, etc. I’ll show examples of the content these contain in future posts with other diseases. Additionally, we will look at a graph labeled ‘Marker Effects’. This graph shows the approximate effects of my genotype at the 12 reported markers for Crohn’s.<br /><br />The 23andMe website content is designed to be mostly educational. This is a key point for customers to understand. Sure I saw my genetic results, but the majority of the menu choices and screens provided me with information to help me understand the disease(s), and how genetics plays a role in the development of the disease. Because my clinical knowledge is extremely limited (I’m an IT guy), I found the educational materials to be very important, sometimes even more important than my actual genetic information. There is a lot more content from my report to share in future posts. We’ll continue this fantastic journey next time.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg_469ykM_xAw2HHFPI6a7bzDWZkC-sETvWb6zNEXMu_IyKFnlKDzcSX-zcvaaznr-aFqYB38P2jZXdAhgrSuYrkez4yVrDJgdLs_9-yYO11oF1dCcNV8h7WnMMPds2iMS6iUFGlRkAnILF/s1600-h/MarcSWilliams-thumb.jpg"><img id="BLOGGER_PHOTO_ID_5341272521423463202" style="FLOAT: left; MARGIN: 0px 10px 10px 0px; WIDTH: 78px; CURSOR: hand; HEIGHT: 78px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg_469ykM_xAw2HHFPI6a7bzDWZkC-sETvWb6zNEXMu_IyKFnlKDzcSX-zcvaaznr-aFqYB38P2jZXdAhgrSuYrkez4yVrDJgdLs_9-yYO11oF1dCcNV8h7WnMMPds2iMS6iUFGlRkAnILF/s320/MarcSWilliams-thumb.jpg" border="0" /></a><br /><br /><strong>Perspective from a medical geneticist</strong><br /><br /><br /><strong>Crohn's disease risk</strong><br /><br />In our previous posts, we’ve written our sections independently in order to try and present our views without any bias that could influence the content. Now that we are diving into Grant’s results, we are going to change. As you may recall in our first post, one of the things we discussed was how this information could be used to inform interactions with medical professionals. With that goal in mind, we thought it important for Janet and me to see Grant’s impression so that we could specifically address any medical questions that arose in his interpretation of the results. In this way we hope not only to reflect both consumer and medical perspectives on the results but also to explore the interaction between the consumer and the health care system, given that 23andMe instructs customers to discuss any changes in health behavior with their provider.<br /><br /><strong>Informed Patient</strong><br /><br />As I read Grant’s post, my first thought was, wow, I wish all of my patients had this level of insight into risk!! One of the most challenging things in practice is trying to convey concepts of probability and risk. It’s not something most of our brains are very good at. If they were we wouldn’t have Las Vegas and lotteries.<br /><br />Grant immediately focused on his elevated risk for certain conditions—a very natural reaction. Crohn’s disease jumped out from the list as the relative risk is 3-fold greater than average. What impressed me was how quickly Grant moved from that concept to the more relevant concept of absolute risk—that is, how likely am I to actually develop the disease? In my practice experience a lot of time is spent explaining these concepts with less than satisfactory results.<br /><br /><strong>Just-in-Time Clinical Knowledge</strong><br /><br />One of the innovations in the 23andMe website is the ability for customers to readily access information that is specific to the question at hand. Grant wasn’t sure exactly what Crohn’s disease was but he was able to click on a link that took him to a brief descriptive paragraph about Crohn’s disease. Embedded in the paragraph are hot links that can provide definitions of concepts that may not be clear. Links are given for those who desire more information. This educational approach is sometimes called “just-in-time”. It is a very sophisticated way to present information to people when they are ready to learn. One of my areas of interest is how the electronic health record can be used to present specific and relevant information to clinicians at the point of care. We’ve been exploring these types of just-in-time strategies to see if that leads to improvement in care. I don’t know if part of 23andMe’s research strategy is to explore the effectiveness of these educational messages, but I hope they spend some time on this as we have a lot to learn.<br /><br /><strong>Odds Calculator</strong><br /><br />The Odds Calculator is also really cool. In most counseling situations I can’t customize the risks I’m presenting to my patients because I don’t have ready access to all of the information that impacts risk and don’t have the ability to compute the interactions in such a way as to be relevant to the specific patient. The Odds Calculator does this and as Grant noted, his customized absolute risk is much lower than the general risk information presented on the first screen. Now one must assume that the results given by the Odds Calculator is based on good data and knowledge of the interaction between factors. It is after all a black-box—we can’t look under the hood to check the calculator’s math. If a patient came to me and asked about the accuracy of this risk estimate, I would want to know all of the data used, the assumptions made and the literature it was based on to be able to provide a good answer. In general discussion with genetic and non-genetics colleagues, all bemoan that fact that we for the most part aren’t able to provide specific risk information for our patients.<br /><br /><strong>The SNP Train</strong><br /><br />So how did 23andMe conclude that Grant’s relative risk was 3.01? That, it turns out did not involve a black box. 23andMe reported information on Adjusted Odds Ratios for 12 Single Nucleotide Polymorphisms (SNPs) for which there are reports associating the SNP with Crohn’s disease. Multiplying these Adjusted Odds Ratios together gives a result of 3.04—not different from 3.01. The assumption here is that all of these SNPs independently contribute to Crohn’s risk. This assumption is unproven. For example, three of the SNPs reside in a single gene, NOD2. This raises the question of whether these SNPs travel completely independently, or if they may be linked together so the pattern of SNPs is not random. Let’s use the analogy of a railroad, with an individual car representing a SNP. Looking at the 3 trains in the middle of the track; if the coal car of the top train, the Sinclair tanker of the middle train and the caboose of the bottom train were SNPS, we could most likely treat them as independent since they would all head out to different destinations. However, if the 3 SNPs in NOD2 are in linkage, then they would travel together as the coal car, tanker and caboose would in the train that is on the track. Thus they aren’t independent and the risk conferred by an individual SNP cannot be said to contribute an independent risk.<br /><br /></div><img id="BLOGGER_PHOTO_ID_5357943079360311490" style="DISPLAY: block; MARGIN: 0px auto 10px; WIDTH: 440px; CURSOR: hand; HEIGHT: 198px; TEXT-ALIGN: center" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjWfd84wVGxDAaSD1HIT_rpRheQkNNmOTvO4XrDk332jhvdRDPs_6f9JckxmILlS2KzFpXCQKff82Aj9RLpbpXx8OE2FFp_fU2BFjEqwP9oeLDbtxraGIBsOb6CJ0ORYyJJuSLeawduUWsS/s800/train+analogy-1.JPG" border="0" /><br />Combinations of SNPs that travel together are called haplotypes. Haplotypes are increasingly favored for risk prediction because it is easier to address the independence of haplotypes. What I did like was the brief description of what is known about each SNP in relation to Crohn’s disease and the reference list associated with each. It would be great to have a clearinghouse of information like this available as it would be easy to gather necessary information and references quickly when a question arose. That said, I don’t think I’ll cough up (spit up?) the coin to have my genome run just to get access to the information. It is hard to know how useful this information will be to customers.<br /><br /><strong>Understanding Environmental Factors</strong><br /><br />Finally Grant noted the contribution of environmental factors to the development of Crohn’s disease. If I were counseling Grant (and I guess I am) I would point out that his understanding of the role of genes and environment is not strictly accurate at least as stated. Grant indicates that “If only half of the cases of Crohn’s can be attributed to genetics, then half get the disease for reasons other than genetics!” Actually what is trying to be conveyed is that cases of Crohn’s disease are likely due to a combination of genetic and environmental factors and, on average, half of the factors are genetic and half are environmental. In other words, one can’t divide Crohn’s into two piles, one genetic and one not.<br /><br /><strong>How Your Doctor Will Respond</strong><br /><br />This leads to the question of how can Grant use this information? Clearly at the present time he’s stuck with the genes he inherited from his parents. So if this information is going to be useful, Grant would have to modify his environment (meaning his relevant behaviors related to the environment) to reduce risk. In the information provided about Genes vs. Environment (and I would not have used vs.) 23andMe states, “…environmental factors are currently unknown.” This means that there is nothing to do to modify Grant’s risk based on present information. So does this information have value? Certainly not if Grant wants to avoid the disease given that he can’t modify his genetic predispositions and we don’t presently know what he should change in his environment. One could argue that if symptoms of diarrhea, weight loss, cramping, etc. were to develop mentioning the increased relative risk for Crohn’s disease could lead to more expeditious diagnosis and treatment. However, it could also lead away from another diagnosis causing delay in diagnosis in treatment. The truth is we don’t know whether this is valuable or not. This position was reinforced in the MD’s Perspective section provided by Dr. Melvin Heyman.<br /><br /><img id="BLOGGER_PHOTO_ID_5357943679689646162" style="DISPLAY: block; MARGIN: 0px auto 10px; WIDTH: 440px; CURSOR: hand; HEIGHT: 92px; TEXT-ALIGN: center" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi02qT2iAU6VTQgPuxeuAs_PlXq0DjvfkEVOeJjVjE0SVp44HbiXrV-wAPWoSP1zGhd6tIuFUzoEB0MA9CE8CPET2TVSsDbmGKw_khbdUQdGFsgZBNDKp54mi2TVUu91JkqKoNPo6Er4CpZ/s800/Crohn's+MD+Perspective-1.jpg" border="0" /><br /><p>(The following is an excerpt from this section.)<br /><br /><span style="font-family:verdana;color:#666666;"><em><strong><span style="color:#333333;">23andMe:</span></strong> Historically, how have doctors used genetics and family history when predicting a patient's risk of developing Crohn's Disease?<br /><strong><span style="color:#333333;">Dr. Heyman:</span></strong> The closest doctors have come is to look at family history for initial clues when given a set of symptoms. If a patient presents with symptoms suggestive of Crohn's Disease, such as abdominal pain, weight loss, poor growth in a child, or fever, a positive family history might lead to further testing faster compared to a situation where the family history is negative.<br /><strong><span style="color:#333333;">23andMe:</span></strong> Recent genome-wide association studies have enabled scientists to identify genetic markers associated with increased risk of Crohn's Disease. How do you think this information can be put into clinical practice?<br /><strong><span style="color:#333333;">Dr. Heyman:</span></strong> Again, until further studies are done to show the clinical utility of a genetic test, a recommendation for clinical practice is premature. However, in the future, such testing might help a doctor decide how aggressively to evaluate a patient for Crohn's Disease if symptoms develop. More research and clinical studies need to be performed before genetic markers for Crohn's Disease can be used to inform clinical practice.<br /><strong><span style="color:#333333;">23andMe:</span></strong> If I had the riskier versions of the SNPs known to be associated with Crohn's Disease, what would you suggest that I tell my personal physician?<br /><strong><span style="color:#333333;">Dr. Heyman:</span></strong> Because of the lack of clinical studies, we do not currently use genetic information when assessing a patient’s risk of developing Crohn's Disease. As the genetic and clinical research advances, we hopefully will reach a point where this information can be useful for patients and doctors. However, in these early stages, the main message to provide to your personal physician is this: Be aware that these genetic markers may indicate future development of Crohn's Disease.</em></span></p><p>Dr. Heyman clearly indicates that clinicians do not use genetic information for assessing risk for Crohn’s at the present time although indicates that this may change in the future. I appreciate 23andMe’s willingness to publish an independent perspective that doesn’t oversell the tests’ usefulness. Dr. Heyman does note the importance of family history in assessing risk. Family history captures not only genetic predispositions running in families, but also shared environment that confers additional risk. Grant is aware of a cousin who has Crohn’s disease. A relative such as this (that is beyond a second degree relative) doesn’t significantly increase risk for any disease.<br /><br /><strong>Final Word</strong><br /><br />So if Grant were to ask me what he should do with regards to his increased risk for developing Crohn’s disease I would say, check back periodically to see if we’ve learned anything about environmental factors. Until then check out your prostate!! (Glimpse of coming attractions)<br /><br />There are lots of innovative ideas about information sharing that are being deployed in the 23andMe site. I’m going to be learning a lot as we continue to explore Grant’s genome.</p><p><strong>Read the next post - <a href="http://exploringmygenes.blogspot.com/2009/07/carrier-status-do-you-have-your.html">Carrier Status – Do you have your tracking number?</a></strong></p>Grant M. Woodhttp://www.blogger.com/profile/18185402177712853914noreply@blogger.com4tag:blogger.com,1999:blog-1887866819730206489.post-57990723622042473452009-06-29T06:45:00.025-06:002009-09-08T12:18:47.554-06:00Research 2.0 - For the genetic extrovert in all some of usIdentifying the ‘gene-which-senses-danger-ahead’ was not part of the 20+ traits my 23andMe genetic service report promised to include. I think lacking that gene is true for all of us who have consented to allow 23andMe to use our genetic information to conduct the 23andMe authorized scientific research. I prefer to claim I have the adventurer/explorer gene - it sounds more glamorous.<br /><br /><strong>The New Open Paradigm</strong><br /><br />My first exposure to the concept of sharing personal medical information was a website called <a href="http://www.patientslikeme.com/">PatientsLikeMe</a>. The purpose of this site is to give people diagnosed with life-changing diseases a forum to share medical information that potentially can improve the lives of others. The website creators plan to share this self-reported health information with doctors, pharmaceutical and medical device companies, and research organizations. The theory - as stated on the site - is that “openness is a good thing”. They continue with “when patients share real-world data, collaboration on a global scale becomes possible. New treatments become possible. Most importantly, change becomes possible”.<br /><br />I was changed in my opinion of the benefits of "openness" as I read the very personal stories of people from around the world. One example was a mother with a young child from South Africa. Just when she thought life was going well, she was diagnosed with Parkinson’s disease. This mother publicly tracks treatments, medications, and supplements on the PatientsLikeMe website, and shares how effective they are. She also reports daily or weekly on symptoms like insomnia, anxiety, and even sexual dysfunction.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjgcfgBlUbcQrpWlYQ4YsOYcHWco_EygvQznCXeAf2nefkHo_j38oXVQnpEqNlKKdegGaYiq-1TKeKn_8ANomCIr0Edr1lTWmqf9GEpon3uRLl-L-gkvMYIVQkwoeyM7B3cssey6lqs1c83/s1600-h/research.JPG"><img id="BLOGGER_PHOTO_ID_5352622077660174594" style="FLOAT: left; MARGIN: 0px 10px 10px 0px; WIDTH: 236px; CURSOR: hand; HEIGHT: 32px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjgcfgBlUbcQrpWlYQ4YsOYcHWco_EygvQznCXeAf2nefkHo_j38oXVQnpEqNlKKdegGaYiq-1TKeKn_8ANomCIr0Edr1lTWmqf9GEpon3uRLl-L-gkvMYIVQkwoeyM7B3cssey6lqs1c83/s320/research.JPG" border="0" /></a><br /><br /><br /><strong>What is Research 2.0</strong><br /><br />I was already sold on the idea of sharing personal health information by the time I read that 23andMe consents all of its customers to participate in “a new kind of research that has the potential to produce valuable insights more quickly and less expensively than traditional methods". They call it Research 2.0, because "this new approach lets you initiate, advise and participate in research via the Internet".<br /><br />Some of the major points I read in their research policies include:<br /><br />1. 23andMe would not reveal my identity.<br />2. 23andMe would share the results of all research and show me how my contributions were making an impact.<br />3. The idea is to make possible large studies that would not be feasible using current methods.<br />4. The research will discover new genetic associations that could shed more light on my data, but without me expecting any financial benefit as a result of having my genetic data processed or shared with research partners, including commercial partners.<br />5. Nothing would be released to any outside company without my explicit consent.<br />6. 23andMe will continually update me about ongoing company sponsored research and let me know of other opportunities to get involved with research in genetics.<br />7. 23andMe intends to publish robust results of scientific studies that they conduct or that are conducted with their research partners.<br /><br /><strong>Similiar Projects</strong><br /><br />Another high profile effort that is following this same philosophy is the <a href="http://www.personalgenomes.org/">Personal Genome Project</a> (PGP), led by George M. Church, PhD, Professor of Genetics at Harvard Medical School. PGP is "building a framework for prototyping and evaluating personal genomics technology and practices at increasing scales". The major difference with 23andMe is that the PGP will do full genome sequencing (all of my DNA), as opposed to the 0.008 percent (or less than 1 in 10,000) of my DNA that 23andMe tests for. Of course, a $399 23andMe service is comparatively more affordable, whereas a full PGP genome scan costs in the tens of thousands of dollars, and is therefore subsidized for those who must complete a selection process.<br /><br />Dr. Church did a great television interview describing his vision of Research 2.0 on the <a href="http://www.charlierose.com/view/interview/10399">Charlie Rose program</a>. The founders of 23andMe, Linda Avey and Ann Wojcicki, were also interviewed. As the cornerstone of their research, the Personal Genome Project is recruiting "individuals interested in obtaining and openly sharing their genome sequences, related health and physical information, and reporting their experiences as a participant of the project on an ongoing basis". I think I have the right gene for that. Sign me up!<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg_469ykM_xAw2HHFPI6a7bzDWZkC-sETvWb6zNEXMu_IyKFnlKDzcSX-zcvaaznr-aFqYB38P2jZXdAhgrSuYrkez4yVrDJgdLs_9-yYO11oF1dCcNV8h7WnMMPds2iMS6iUFGlRkAnILF/s1600-h/MarcSWilliams-thumb.jpg"><img id="BLOGGER_PHOTO_ID_5341272521423463202" style="FLOAT: left; MARGIN: 0px 10px 10px 0px; WIDTH: 78px; CURSOR: hand; HEIGHT: 78px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg_469ykM_xAw2HHFPI6a7bzDWZkC-sETvWb6zNEXMu_IyKFnlKDzcSX-zcvaaznr-aFqYB38P2jZXdAhgrSuYrkez4yVrDJgdLs_9-yYO11oF1dCcNV8h7WnMMPds2iMS6iUFGlRkAnILF/s320/MarcSWilliams-thumb.jpg" border="0" /></a><br /><br /><strong>Perspective from a medical geneticist</strong><br /><br /><br /><br /><strong>A New Research Model</strong><br /><br />For those of you anxious to dive into Grant’s DNA, please accept my sincere apologies for one more delay. I thought it important to spend some time (probably more than was needed) to explore some of the information and decisions prior to proceeding with testing. This will be the last hors d’oeuvres prior to the main course.<br /><br />One of the intriguing aspects of the 23andMe service is the opportunity to participate in a variety of research endeavors—named 23andWe. This approach is called Research 2.0 by the company and could be fairly characterized as direct-to-consumer research. The idea is to collect not only DNA but information from 23andMe consumers using surveys and link the data. Currently there are 23 different surveys available on the site. Surveys are optional for participants.<br /><br />Once again there is a marked contrast between this approach and the traditional medical research model I am familiar with. One of the most positive aspects relates to sharing research results. Many of my patients become upset when they learn that I am prohibited from returning research results directly to them because of federal research oversight regulations, and quite frankly I’m not too happy about it either. It doesn’t seem like the right thing to do. Given its funding, 23andWe is not subject to these restrictions and they state, “…we will share the results of all research and show you how your contributions are making an impact.”<br /><br />This is an excellent way to engage and maintain involvement of their community. They also clearly outline the entire research process from proposal to publication. This pulls back the curtain on what is needed to conduct scientifically valid research—something that the general public usually doesn’t see. They also commit to keeping participants informed about the current status of the research project. Having enrolled many patients in a variety of research projects, I have certainly been frustrated by the apparent black hole that collects information and samples, yet returns nothing to my universe. This does not respect the sacrifice that our patients make to participate. Kudos to 23andMe for their commitment to information exchange.<br /><br />In contrast, viewed through my pervasive paternalism there are some concerns as well. Many of these surround issues of privacy and information sharing that I discussed in the last post, so I will not reiterate those here. There are a couple of areas that do deserve additional comment.<br /><br /><strong>Research Oversight</strong><br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgll2zNaKyuN4s95TwsAgTRMy-x15cITuWJo0NF9jOGZMDGENQvxMM8zg1VADWbIdZuNtMDg2mmBc_oPwFFaO6lQ9tfOx56KWzRzt-KJEy-6Nngo-EWeq8lj3V_X_HUforRTu9dW5aUkW6l/s1600-h/16th+century+medicine.jpg"><img id="BLOGGER_PHOTO_ID_5352924009788208002" style="FLOAT: right; MARGIN: 0px 0px 10px 10px; WIDTH: 225px; CURSOR: hand; HEIGHT: 163px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgll2zNaKyuN4s95TwsAgTRMy-x15cITuWJo0NF9jOGZMDGENQvxMM8zg1VADWbIdZuNtMDg2mmBc_oPwFFaO6lQ9tfOx56KWzRzt-KJEy-6Nngo-EWeq8lj3V_X_HUforRTu9dW5aUkW6l/s320/16th+century+medicine.jpg" border="0" /></a>That there is a need for oversight of human subjects research is an unfortunate legacy of unsound, unethical and in some cases heinous acts performed in the name of medical research. Names like Mengele, Tuskegee syphilis study and Unit 731 have resulted in national and international standards for conduct of human subjects’ research. In the US, the Office of Human Research Protection (OHRP) provides leadership in the protection of the rights, welfare and wellbeing of all subjects of research conducted or funded by the Department of Health and Human Services. OHRP and related organizations have promulgated rules and regulations that establish Institutional Review Boards, Privacy Boards, Patient Safety and Adverse Event committees to ensure as best as possible that research is conducted according to the highest scientific and ethical standards. Since they are privately funded, 23andWe is not subject to regulatory oversight for their research. There are some important differences in procedures that are worth highlighting.<br /><br /><strong>Consent</strong><br /><br />Subjects entering a research project must give consent to participate. The process of giving this consent usually requires the subject to read a consent document in the subject’s primary language (or with the aid of a certified translator) and at an appropriate readability level. The document outlines the nature of the study, the subject’s involvement, potential benefits and harms, disposition of information and biologic samples, rights and researcher contact information. A member of the research team is present to answer any questions. These consents are specific to a given project--that is if a subject enrolls in more than one project, a separate consent is required for each. In the case of 23andWe it appears that if one submits a sample and completes surveys, this information is subsequently available to any and all research activity approved by 23andWe. In navigating through the different surveys, no information was provided with the individual survey regarding how the information was to be used. Other than choosing which surveys to fill out there doesn’t appear to be any way for a 23andWe participant to participate in some research projects and not others.<br /><br /><strong>Conflict of Interest</strong><br /><br />Regulated research requires explicit disclosure of funding as well as declaration of any potential conflict of interest. 23andWe indicates that all research must be reviewed by 23andMe’s “…internal and external review committees…for scientific and ethical merit, as well as potential interest to the 23andMe community.” In reviewing the various ongoing research projects on the website I was unable to find any specific information about the composition of these committees, nor any disclosures. They do acknowledge in the Privacy Statement that they (23andMe) may receive compensation from these research partners. The information on the Parkinson disease study notes that 23andMe received funding from the Michael J. Fox Foundation for Parkinson’s Research. No other funding disclosures were identified.<br /><br /><strong>Inducement</strong><br /><br />Historically this issue was raised in the context of inducing individuals such as prisoners to engage in research with the promise of decreasing the length of their sentence. It has since expanded to include monetary compensation for subjects beyond covering expenses associated with the research and a modest honorarium. The ethical issue is to avoid tempting someone to participate in research that they would not otherwise choose. For most 23andWe participants this is not an issue, as they are actually paying to participate in that they have to purchase the test. However, in the case of the Parkinson’s disease study the cost of the 23andMe test is only $25 as opposed to $399 due to generous underwriting by Google co-founder Sergey Brin. I certainly can’t say if this would fall outside limits applying to regulated research, but it should be noted that those patients with Parkinson’s who participate will be participating in all 23andWe sponsored research, not just the Parkinson’s project as I could not find any information on the site limiting this participation.<br /><br /><strong>The Science</strong><br /><br />This is a new research model, and it remains to be seen if the model will perform as envisioned. I look forward to seeing the methods and results of the research published and hope that this does increase the pace of discovery as hoped.<br /><br />In her address to the Secretary’s Advisory Committee on Genetics, Health and Society, Katie Hood, the CEO of the Michael J. Fox Foundation for Parkinson’s Research (the largest private funder of Parkinson’s research in the world) in discussing the foundation’s partnership with 23andMe eloquently expressed the frustration of affected individuals with the slow pace of research, as well as the challenge of competing for limited research dollars. By using their resources to create research partnerships and offering these directly to affected members through services such as 23andMe, they hope to fulfill their mission of driving the best Parkinson’s research in order to discover improved therapies and a cure. I for one hope they succeed.<br /><br /><p><strong>Read the next post - <a href="http://exploringmygenes.blogspot.com/2009/07/grand-opening-looking-inside-my-genetic.html">The Grand Opening - Looking Inside My Genetic Crystal Ball</a></strong></p>Grant M. Woodhttp://www.blogger.com/profile/18185402177712853914noreply@blogger.com0tag:blogger.com,1999:blog-1887866819730206489.post-40872272425834907342009-06-15T06:45:00.010-06:002009-09-08T12:18:06.789-06:00Reading about Consents, Risks, and Privacy - Now the Fun Starts<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhRuDqJ07Jc4LnXcq0Tcflb1MsLYod8nbLkileNnD_HgproEv0sjV7Y97SOGlhc5JpV0peaiMoTHcVKzTlP8xYsKBdLM8k5FdajAFJU4UcuqaP3m6FWAfKICP0g3M-_oBe1_6gwAkaLY2NU/s1600-h/IMG_1175.JPG"><img id="BLOGGER_PHOTO_ID_5347258914289124242" style="FLOAT: left; MARGIN: 0px 10px 10px 0px; WIDTH: 176px; CURSOR: hand; HEIGHT: 132px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhRuDqJ07Jc4LnXcq0Tcflb1MsLYod8nbLkileNnD_HgproEv0sjV7Y97SOGlhc5JpV0peaiMoTHcVKzTlP8xYsKBdLM8k5FdajAFJU4UcuqaP3m6FWAfKICP0g3M-_oBe1_6gwAkaLY2NU/s320/IMG_1175.JPG" border="0" /></a> I remember how excited I was when the test kit arrived in the mail. It felt so new millennium. Ordering the test online was in fact easier than buying an airline ticket - and compared to many fares, even less expensive! I was also lucky that the Utah Department of Health officials were not overly zealous like those from <a href="http://www.wired.com/wiredscience/2008/06/23andme-were-no/">New York and California</a>. I was still allowed the choice to investigate my biology on my own terms. But 23andMe made sure I read several pages of Consent, Risk, and Privacy policies before the order could be completed.<br /><br /><strong>The Consent and Waiver section</strong><br /><br /><strong>“23andMe's service is not a test or kit designed to diagnose disease or medical conditions, and it is not intended to be medical advice.”</strong> This is probably the most important statement to be aware of. In other words, don’t make your own diagnosis, and don’t print your report and expect your doctor to review the entire thing with you. Another declaration includes “… accessing your genetic information through 23andMe does not translate into a personal prediction”. As you read further you learn that other disease factors are environmental and not genetic, that our understanding of genetically influenced disease may be incomplete, and that gene/disease associations are based on populations and not individuals.<br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhnDD1Kgl614LTSgt2XgW5OFR5Mm_mohnRLynAIgeBDL74AmEfAYqvpqayVOMkTqKj3s_25yFDjO62bbdLoB8UdN07oe45q6sq0kCkAI6BQPcBwQzW_6756GJBHzx1Fq-dZ88deMaGZnCxf/s1600-h/ride.jpg"><img id="BLOGGER_PHOTO_ID_5347434531818840914" style="FLOAT: right; MARGIN: 0px 0px 10px 10px; WIDTH: 185px; CURSOR: hand; HEIGHT: 259px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhnDD1Kgl614LTSgt2XgW5OFR5Mm_mohnRLynAIgeBDL74AmEfAYqvpqayVOMkTqKj3s_25yFDjO62bbdLoB8UdN07oe45q6sq0kCkAI6BQPcBwQzW_6756GJBHzx1Fq-dZ88deMaGZnCxf/s320/ride.jpg" border="0" /></a><strong>The Risks section</strong><br /><br />This section presented statements about risks I might be exposed to by using the service.<br /><br /><strong>“You may learn information about yourself that you do not anticipate.”</strong> Isn’t this true for any medical information we get as part of receiving healthcare services? Besides, I’ve already heard some interesting positive stories from what others have learned from their genetic test. For some reason I don’t have any fears of what I might learn, so no worries for me here.<br /><br /><strong>“The laboratory process may result in errors.”</strong> Errors? In healthcare? With our advanced technology? That never happens. (Just joking). Again, not worried.<br /><br /><strong>“You should not change your health behaviors on the basis of this information.”</strong> I’m male, so I’m genetically predisposed to difficulty with changing behavior. Add to that the fact that I’m single. I think I need to get a wife first to ‘encourage’ me change. For men with wives, don’t show them your test results. (To anticipate questions as to why I’m single - I do have the commitment gene, just not the lucky in love gene.)<br /><br /><strong>“Genetic research is not comprehensive and future scientific research may change the interpretation of your DNA.”</strong> This simply means we do not have all the answers yet. Everybody should understand this. Actually, this just means job security (which today is worth its weight in gold).<br /><br /><strong>“Genetic data you share with others could be used against your interests.”</strong> One option of the service is to share your results with other 23andMe customers. This is done by one person sending a share request to another, and the receiving person accepting or rejecting the offer. Obviously, I‘ve already decided to be all-in on the sharing business. Besides, I agree with an article that appeared in the London Times titled “<a href="http://www.timesonline.co.uk/tol/news/uk/science/article6374136.ece">Our genetic code should be no big secret </a>".<br /><br /><strong>“23andMe Sponsored Research: We will analyze your genetic and other voluntarily contributed personal information as part of our scientific research with the purpose of advancing the field of genetics and human health.”</strong> I think many service customers will see this as a bonus. We want to volunteer, as it makes us feel we are part of something greater than ourselves.<br /><br />And finally, <strong>“Collaborative Research will be de-indentified”.</strong> The collaborative research with this blog will be completely identified of course. We have to keep it interesting.<br /><br /><strong>The Privacy section</strong><br /><br />This section informs the customer about the choices they have related to their private data.<br />• Participation in activities and services that involve personal information beyond initial account and Genetic Information is voluntary and permission-based.<br />• It is entirely within your discretion to provide information or answer survey questions.<br />• At your request we will delete your account and personal information linked to your account from our systems.<br /><br />My first thought was I don’t need any more protection than this. I guess I will find out if that’s true or not. I have to admit though that I read all of this privacy stuff because I knew Dr. Williams would ask me if I did.<br /><br />So after reviewing and contemplating the consequences, I opened the box, spit in the tube, and sent it off. A more detailed description of this step will be in the next blog. My DNA would not come back in the mail, but would be converted into electronic bits and travel over the Internet. What a futuristic voyage.<br /><br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg_469ykM_xAw2HHFPI6a7bzDWZkC-sETvWb6zNEXMu_IyKFnlKDzcSX-zcvaaznr-aFqYB38P2jZXdAhgrSuYrkez4yVrDJgdLs_9-yYO11oF1dCcNV8h7WnMMPds2iMS6iUFGlRkAnILF/s1600-h/MarcSWilliams-thumb.jpg"><img id="BLOGGER_PHOTO_ID_5341272521423463202" style="FLOAT: left; MARGIN: 0px 10px 10px 0px; WIDTH: 78px; CURSOR: hand; HEIGHT: 78px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg_469ykM_xAw2HHFPI6a7bzDWZkC-sETvWb6zNEXMu_IyKFnlKDzcSX-zcvaaznr-aFqYB38P2jZXdAhgrSuYrkez4yVrDJgdLs_9-yYO11oF1dCcNV8h7WnMMPds2iMS6iUFGlRkAnILF/s320/MarcSWilliams-thumb.jpg" border="0" /></a><br /><br /><strong>Perspective from a medical geneticist</strong><br /><br /><br /><br /><strong>Caveat Emptor!!</strong><br /><br />I have a confession to make. I don’t read all the end user agreements that come with my software and computers. For all I know representatives from a software company could show up at my door informing me that I agreed to pick grapes in Sonoma. Bill Gates may have a lien on my spleen!! My approach to the ubiquitous end user agreement is best summed up in the words of Blanche DuBois, “Whoever you are, I have always depended on the kindness of strangers.” I can only hope it turns out better for me than Blanche.<br /><br />Seriously, the problem of the end user agreement is not a trivial one. Many view them as contracts of adhesion—essentially a take it or leave it agreement where the purchaser has no leverage with which to negotiate with the seller. So how does this relate to direct-to-consumer genetic tests? In order to purchase the service the user must agree to certain things. In the case of 23andMe the purchaser must agree to both consent and waiver and terms of service. I certainly don’t have the background to determine whether these documents meet the criteria to be called contracts of adhesion, but there are some points I think worth considering, particularly given the concern that the public has expressed about privacy of medical and genetic information.<br /><br /><strong>General issues</strong><br /><br />I reviewed three documents from 23andMe; the privacy statement, the consent and waiver and the terms of service. These documents were respectively 8, 6 and 13 pages long, the last printing in 9 pt. type. I imported the first two into Word and ran the readability statistics package. The ease of reading was 31.6 and 34.4 (target being in the 60-70 range) and grade level was nearly 14. Medicare requires that its patient materials have a readability grade level of 5, and most health educators recommend nothing higher than 8th grade reading level for patient-directed material. This raises the question of how well the materials are understood by the reader (recognizing that in many if not most cases, the documents aren’t even read). As I sit here in my glass house heaving rocks the reader should know that the ease of readability of this post is 41.6 with a grade level of 13.4.<br /><br /><strong>Potential contradictions</strong><br /><br />In the privacy statement, 23andMe states that, “We will not release your personal information to any outside company without your explicit consent.” Given my experience with HIPAA, medical records and research, I would interpret that to mean that I will be asked to give my consent for this information to be released each time. However, that explicit consent seems to reside in the terms of service which states in clause 9: “…you acknowledge and agree that 23andMe is free to preserve and disclose content to non-profit or commercial partner organizations conducting scientific research…” Finally in the research section of the consent and waiver it states, “We will analyze your genetic and other voluntarily contributed personal information as part of our scientific research with the purpose of advancing the field of genetics and human health.” As best as I can determine, by sending in your saliva you are giving <strong>explicit</strong> consent to contribute your DNA results to any and all research approved by 23andMe. If you add any information to your profile such as a health condition, age, weight, ethnicity, survey result etc. you have now given <strong>explicit</strong> consent for that to be added to the data available for release. This consent extends indefinitely unless you close your account at which time your information is removed from their database, however regarding any information already sent to outside collaborators “…we cannot guarantee that it will be destroyed upon request.” (Consent and waiver—Collaborative Research)<br /><br /><strong>Saliva sample</strong><br /><br />In the privacy document under Genetic Information it states, “…DNA and saliva samples are destroyed after the laboratory completes its work…” However, in the terms of use in clause 17 it states, “Your saliva, once submitted to and analyzed by us, becomes our property.” (this is repeated in clause 18). The destruction of the sample is <strong>not</strong> referenced at all in the terms of service. As I understand it, the privacy statement has no legal standing—only the consent and waiver and terms of service.<br /><br /><strong>Promises, promises</strong><br /><br />So what is really warrantied by 23andMe? From clause 3 of the terms of service (the omissions are not intended to disrupt the context): “…genetic information you receive…cannot be relied upon at this point for diagnostic purposes…Genetic discoveries…have not, for the most part been clinically validated…and the technology…has also not yet been validated for clinical utility.”; “…our testing service is not licensed by the relevant state and federal authorities for genetic testing conducted for health and disease-related purposes. Reliance on any information provided by 23andMe, 23andMe employees, others appearing on our website at the invitation of 23andMe, or other visitors to our website is solely at <em>your own risk</em>.” (Emphasis added) From clause 19 (Disclaimer of Warranties, which by the way is all capitalized which is known to reduce readability, so I eliminated them in this post): “…23andMe makes no warranty that…the service will be…unfailingly secure, or error-free…results …of the service will be accurate or reliable…any errors in the software will be corrected…23andMe specifically disclaims any liability with regard to any actions resulting from your participation in the service.”<br /><br /><strong>Felons beware</strong><br /><br />23andMe in both its privacy statement and terms of use notes that it will disclose your information “…pursuant to judicial or other government subpoenas, warrants, or orders.” (insert your Bill Clinton joke here) This has been a concern for creators of DNA databases and in fairness there are no standards to guide anyone with regards to requests from law enforcement seeking to match a DNA specimen obtained at a crime scene to a DNA database.<br /><br /><strong>What’s new with you?</strong><br /><br />We all know that genetic knowledge changes rapidly. Will you be able to take advantage of this new knowledge—given that you may have contributed to generation of this knowledge through the 23andMe research program? According to clause 13 of the terms of service the answer is: “You acknowledge that 23andMe may offer different or additional technologies to collect genetic data in the future and that your purchase of our Service today does not entitle you to any different or additional technologies for collection of your genetic data without fee, and you will have to pay additional fees in order to have your genetic data collected on any future or additional technologies.<br /><br /><strong>Bottom line</strong><br /><br />Having now read these documents, I would certainly encourage anyone wanting to purchase the service to read them carefully and seek help for understanding what they say if necessary. I should also note that while I am “picking” on 23andMe in this post, it’s only because they were the service Grant purchased. All direct-to-consumer testing companies have similar end user agreements that deserve scrutiny. Now if you’ll excuse me I have to run home to read all my software agreements!!<br /><br /><p><strong>Read the next post - <a href="http://exploringmygenes.blogspot.com/2009/06/research-20-for-genetic-extrovert-in.html">Research 2.0 - For the genetic extrovert in <del>all</del> some of us</a></strong></p>Grant M. Woodhttp://www.blogger.com/profile/18185402177712853914noreply@blogger.com7tag:blogger.com,1999:blog-1887866819730206489.post-18136323781921904672009-06-01T10:00:00.006-06:002009-09-08T12:16:27.999-06:00What is this all about?Germany recently passed a new law significantly limiting the use of direct-to-consumer (DTC) genetic tests, which can only be carried out by a licensed doctor following the patient’s consent. In response, the UK–based <a href="http://www.phgfoundation.org/">PHG Foundation</a>, an independent not-for-profit public health organization focusing on genome-based science and technologies to improve health, calls this law “a regressive and paternalistic approach that takes genetic exceptionalism to an extreme not seen in other jurisdictions”.<br /><br />Because similar debates are still raging in the US, we decided to explore both sides of the issue. Grant Wood will openly share his results from a DTC genetic service. Dr. Marc Williams will give advice as a medical geneticist and Janet Williams as a genetic counselor. Both will guide Grant through any potential misinterpretations.<br /><br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjIoFaCCVQyQOwXQdqyrXGfV4jo9DjLTc2EQ4Z404j-Pr2F0B-uEnvhJrHi1uUmStoJtD2IoChDi3VNIUvHsPJNT_LuPToAUTqyggz2Ue7ZmwIB1PT2POoaOKffTWjkXh4IXopVsoEZwURD/s1600-h/microarray01.jpg"><img id="BLOGGER_PHOTO_ID_5327578210250859026" style="FLOAT: left; MARGIN: 0px 10px 10px 0px; WIDTH: 103px; CURSOR: hand; HEIGHT: 160px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjIoFaCCVQyQOwXQdqyrXGfV4jo9DjLTc2EQ4Z404j-Pr2F0B-uEnvhJrHi1uUmStoJtD2IoChDi3VNIUvHsPJNT_LuPToAUTqyggz2Ue7ZmwIB1PT2POoaOKffTWjkXh4IXopVsoEZwURD/s320/microarray01.jpg" border="0" /></a> <strong>Influences on my decision<br /><br /></strong><strong></strong><p>Hi. My name is Grant Wood. I work in the field of medical genetics and I consider myself very lucky in that I have a fascinating job. Genetics touches all of us, yet we are still at the point where it has this ring of mystique and futurism to it. In many ways we view genetics as future science; our individual and collective medical future. Genetics is still a relatively new field within healthcare, yet when I tell people about my work, they all want to share stories about a genetic-related condition that has affected them and their families.<br /><br />My work involves building new computer programs that can help doctors and patients collect, track, understand, and use family health history and genetic/genomic information in patient care. Therefore I felt it made perfect sense that I should explore how technology – both gene chips (or <a href="http://en.wikipedia.org/wiki/DNA_microarray">DNA microarrays</a>) and the Internet – could combine to give me access as never before to my own biology.<br /><br />Then another serendipitous event happened. While participating with the <a href="http://www.geneticalliance.org/conf08">2008 Genetic Alliance conference</a>, I spent a day with Linda Avey, co-founder of one of these new personal genomics companies called <a href="https://www.23andme.com/">23andMe</a>, visiting and talking with congressional offices in Washington, DC about the <a href="http://www.genome.gov/24519851">Genetic Information Nondiscrimination Act (GINA) of 2008.</a> I learned that 23andMe provides a service where subscribers can receive personalized genetic reports containing information related to 110 traits and diseases. Order the kit online, spit in the tube, send it in the mail. (More on this in the next post).<br /><br /><p align="center"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh539Ss7_SJUynGqirHjAHdtIUjfOOCxuHZdavF2Gb2FNcmiqSt8Wjl9PdXdBkkdH0wrO5RLQV_6d7KyzIqipiha956TUdydFIk17oMhyPj3HJzERbGtGuPOv-CBYFcgPH1v0QE7an3x0Nd/s1600-h/Speaker's+office.JPG"><img id="BLOGGER_PHOTO_ID_5327591756432952978" style="DISPLAY: block; MARGIN: 0px auto 10px; WIDTH: 320px; CURSOR: hand; HEIGHT: 240px; TEXT-ALIGN: center" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh539Ss7_SJUynGqirHjAHdtIUjfOOCxuHZdavF2Gb2FNcmiqSt8Wjl9PdXdBkkdH0wrO5RLQV_6d7KyzIqipiha956TUdydFIk17oMhyPj3HJzERbGtGuPOv-CBYFcgPH1v0QE7an3x0Nd/s320/Speaker's+office.JPG" border="0" /></a>Linda Avey is in the center. I am on the far left. We are in <align="center">the Speaker of the House's office in the Capitol building, Washington, D.C.</p><p><br />I started to think about what my questions and expectations would be if I decided to sign up for the service 23andMe provided. My list contained questions and thoughts like:<br /><br />• Exactly what kind of information can 23andMe provide me about the 110 traits and diseases my report would cover?<br />• Would I learn something about myself that I didn’t already know?<br />• Would I discover information that I should immediately take to my doctor?<br />• Is genetics really a proven science, and what kind of research is still in progress?<br />• Would it be important for the information in my report to get added to my Intermountain electronic health record?<br />• Should I share this kind of information with my family members? What about other interested people?<br />• What kind of cool technology would 23andMe use to show me my genetic report?<br /><br />The price for the test was high - $999 per test kit - so I put the option of testing on the backburner. A short time after our meeting however, 23andMe reduced the price of their service to $399. I immediately went online and ordered the kit. My journey was about to begin.<br /><br /><br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg_469ykM_xAw2HHFPI6a7bzDWZkC-sETvWb6zNEXMu_IyKFnlKDzcSX-zcvaaznr-aFqYB38P2jZXdAhgrSuYrkez4yVrDJgdLs_9-yYO11oF1dCcNV8h7WnMMPds2iMS6iUFGlRkAnILF/s1600-h/MarcSWilliams-thumb.jpg"><img id="BLOGGER_PHOTO_ID_5341272521423463202" style="FLOAT: left; MARGIN: 0px 10px 10px 0px; WIDTH: 78px; CURSOR: hand; HEIGHT: 78px" alt="" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg_469ykM_xAw2HHFPI6a7bzDWZkC-sETvWb6zNEXMu_IyKFnlKDzcSX-zcvaaznr-aFqYB38P2jZXdAhgrSuYrkez4yVrDJgdLs_9-yYO11oF1dCcNV8h7WnMMPds2iMS6iUFGlRkAnILF/s320/MarcSWilliams-thumb.jpg" border="0" /></a><br /><br /><strong>Perspective from a medical geneticist</strong><br /><br /><br /><br /><br />My First Impressions<br /><br />I'm Dr. Marc Williams. When the first Direct-to-Consumer (DTC) genome tests were made available to the public, my initial response was this is irresponsible and certainly not ready for use. I had concerns that we didn’t have much evidence for the significance of many of the results that were to be reported; we had little information about the accuracy of the testing itself and we didn’t know how to use the information to make recommendations to improve health. In addition people may find out things that they really didn’t want to know as part of the testing (such as finding they carry a mutation in one of the BRCA genes meaning increased risk for breast and ovarian cancer) without access to genetic counseling or that they may pursue expensive investigations based on a finding from testing (as has been seen with whole-body CT scans) that would stress an already overtaxed health care system. These concerns reflect those raised by the American College of Medical Genetics’ <a href="http://www.acmg.net/AM/Template.cfm?Section=Policy_Statements&Template=/CM/ContentDisplay.cfm&ContentID=2975">statement on DTC genetic testing</a>.<br /><br />As I reflected more on this I realized that my initial reaction was in many ways a stereotypical “doctor” response. How dare a patient take medical care into their own hands? In reality we are asking, nay encouraging, patients to take more and more responsibility for their own health and heath decisions. It is hypocritical to encourage patients to take responsibility on one hand and criticize them for doing so on the other. While DTC testing may not be a choice I would make as a patient, I must be willing to accept that others have a different perspective. Consider the example of alternative medicines such as herbal preparations. For a long time physicians scoffed at their usefulness and criticized patients who used them. Ultimately we harmed patients as they would not admit to using alternative medicines to us, rightly fearing criticism, leading to adverse reactions due to interactions with prescription drugs. In addition there is emerging evidence that at least some preparations may be beneficial for certain conditions.<br /><br />If I am open to a patient telling me about the results of their DTC test it allows me to understand what they are concerned about and why. This may provide a teachable moment that will allow the patient to take action to make positive changes in their life. This approach, while not necessarily ‘scientific’ or ‘evidence-based’ reflects our Healing Connections at Intermountain Healthcare, in particular: I listen to you with sensitivity and respond to your needs; and, I treat you with respect and compassion.<br /><br />I look forward to exploring with Grant his journey through his DTC genetic test results. I’m convinced that if I really listen to what Grant has to say, I may learn more from him, than he will learn medically from me. We hope this series will be entertaining and thought-provoking.</p><p><strong>Read the next post - <a href="http://exploringmygenes.blogspot.com/2009/06/reading-about-consents-risks-and.html">Reading about Consents, Risks, and Privacy - Now the Fun Starts</a></strong></p>Grant M. Woodhttp://www.blogger.com/profile/18185402177712853914noreply@blogger.com13