{"id":12276,"date":"2010-03-18T19:08:35","date_gmt":"2010-03-18T19:08:35","guid":{"rendered":"http:\/\/euvolution.com\/futurist-transhuman-news-blog\/snps-for-breast-cancer-risk-it-depends\/"},"modified":"2010-03-18T19:08:35","modified_gmt":"2010-03-18T19:08:35","slug":"snps-for-breast-cancer-risk-it-depends","status":"publish","type":"post","link":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/genetic-medicine\/snps-for-breast-cancer-risk-it-depends.php","title":{"rendered":"SNPs for breast cancer risk? It Depends."},"content":{"rendered":"

\"\"<\/a>I hold in my hot little hands a copy of the NEJM<\/span>, March 18th<\/span> edition. In it there is an article which isn't even released yet.<\/span><\/p>


<\/span><\/div>
Entitled<\/span><\/div>
<\/div>
\"Performance of Common Genetic Variants in Breast-Cancer Risk Models\"<\/span><\/div>

<\/span><\/div>
Remember when we did this for heart disease risk? FAIL WHALE.....<\/span><\/div>

<\/span><\/div>
Do you think it will happen again?<\/span><\/div>

<\/span><\/div>
The Study<\/span><\/div>

<\/span><\/div>
10 common genetic variants<\/span><\/div>

<\/span><\/div>
rs1045485<\/span><\/a><\/div>
rs13281615<\/span><\/a><\/div>
rs13387042<\/span><\/a><\/div>
rs2981582<\/span><\/a><\/div>
rs3803662<\/span><\/a><\/div>
rs3817198<\/span><\/a><\/div>
rs889312<\/span><\/a><\/div>
rs7716600<\/span><\/a><\/div>
rs11249433<\/span><\/a><\/div>
rs999737<\/span><\/a><\/div>

<\/span><\/div>
I had to create a couple of pages on SNPedia<\/span> for this list FYI.....<\/span><\/div>

<\/span><\/div>
The Methods:<\/span><\/div>
Cases and controls-WHI<\/span>, ACS<\/span> CPSII<\/span> Nutrition Cohort, Nurses Health Study, Prostate\/Lung\/Colorectal<\/span>\/Ovarian Cancer Screening Trial, and Polish Breast Cancer Study.<\/span><\/div>

<\/span><\/div>
Cases-Woman who had received diagnosis of invasive breast cancer.<\/span><\/div>

<\/span><\/div>
Risk Models Used-A hybrid of the Gail model.....I.E. Not exactly the Gail Model.<\/span><\/div>
1. First degree relatives with breast cancer<\/span><\/div>
2. Age at Menarche<\/span><\/div>
3. Age at first live birth<\/span><\/div>
4. Number of Breast Biopsies<\/span><\/div>

<\/span><\/div>
They acknowledge that they were unable to get <\/span>atypical hyperplasia<\/span><\/span><\/a> and<\/span> Mammographic<\/span> density. <\/span><\/a>Both of which have improved Gail.<\/span><\/div>

<\/span><\/div>
So, This Gail is a little hobbled and not the best predictive model.......<\/span><\/div>

<\/span><\/div>
The studied models- 5 logistic regression models<\/span><\/div>
I don't have the supplementary tables and methods yet. <\/span><\/div>

<\/span><\/div>
The nongenetic<\/span> model-Gail Model<\/span><\/div>
The Demographic\/Genetic Variant Count Model-included number of alleles.<\/span><\/div>
The Demographic\/Genetic Individual Variant-Accounted for individual effects of each SNP<\/span><\/span><\/div>
The Inclusive Model-Gail, Genetics Demographics<\/span><\/div>
The Demographic Model<\/span><\/div>
And Random....<\/span><\/div>

<\/span><\/div>
When we do these sorts of statistical analyses we look for a couple of things.<\/span><\/div>

<\/span><\/div>
A. Number of people reclassified and how?<\/span><\/div>
B. The Area Under the <\/span>ROC<\/span> Curve<\/span><\/a><\/div>

<\/span><\/div>
The <\/span>AUC<\/span> is a good way of seeing whether a model or test is worthless or useful.<\/span><\/a> And how much MORE useful than another test.<\/span><\/div>

<\/span><\/div>
Results-<\/span><\/div>

<\/span><\/div>
1. The Inclusive Model Yielded and AUC<\/span> of 61.8%<\/span><\/div>
2. The Nongenetic<\/span> Model yielded an AUC<\/span> of 58%<\/span><\/div>
3. The Genetic Individual Variant Yielded an AUC<\/span> of 59.7%<\/span><\/div>
4. The Genetic Variant Count Yielded an AUC<\/span> of 58.8%<\/span><\/div>
5. Breast Biopsy BY ITSELF Yielded an AUC<\/span> of 56.2%<\/span><\/div>

<\/span><\/div>
That is a 3.8% difference in Yield from Genes and without Genes integrated into the weaker Gail Model.<\/span><\/div>

<\/span><\/div>
Lastly, they asked. Well, does this Inclusive Model do a good job of discrimination of High risk vs. low risk.<\/span><\/div>

<\/span><\/div>
The Answer- It determines lower risk better than Gail. It does not determine higher risk better.<\/span><\/div>

<\/span><\/div>
The authors of this study have stated that<\/span><\/div>

<\/span><\/div>
\"As in Diabetes and cardiovascular disease, the addition of the common SNPs<\/span> added little to the predictive value of the clinical models. On the basis of theoretical models, Gail has shown that increases in the AUC<\/span> similar to those observed here and not sufficiently large to improve meaningfully the identification of women who might benefit from tamoxifen prophylaxis or screening mammography\"<\/span><\/div>

<\/span><\/div>
Take Home<\/span><\/div>

<\/span><\/div>
The addition of these factors only creates a minimal statistical increase that is of no useful clinical benefit.<\/span><\/div>

<\/span><\/div>
The Sherpa Says: If the press says \"gene tests fail to improve risk assessment\" You can be assured that the DTCG<\/span> industry is no longer the darlings. If instead they say \"Improvement in risk model\" well, then you have chance to woo them back<\/a>! It Depends.......<\/span><\/span><\/b><\/div>
\"\"<\/div>","protected":false},"excerpt":{"rendered":"

I hold in my hot little hands a copy of the NEJM, March 18th edition. In it there is an article which isn't even released yet.Entitled \"Performance of Common Genetic Variants in Breast-Cancer Risk Models\"Remember when we did this for … Continue reading →<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"limit_modified_date":"","last_modified_date":"","_lmt_disableupdate":"","_lmt_disable":"","footnotes":""},"categories":[5],"tags":[],"class_list":["post-12276","post","type-post","status-publish","format-standard","hentry","category-genetic-medicine"],"modified_by":null,"_links":{"self":[{"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/posts\/12276"}],"collection":[{"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/comments?post=12276"}],"version-history":[{"count":0,"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/posts\/12276\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/media?parent=12276"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/categories?post=12276"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/tags?post=12276"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}