The Confusing Thing About Association Studies.

Today is a moderately slow day for genetics in medicine (I can't believe I just said that). But if you want, you can sell your genome to some stranger for 5 grand USD (I can only imagine the identity theft issues) you do it at your own risk. Listen, if you are hard up for cash please do not sell your DNA sample!! Who knows what they will use it for..........Perhaps to frame you for a crime.

But what I want to really talk about is how confusing association studies can be. So lets examine some of these.

1. Long Term Aspirin use prevents cancer incidence in colon 32%, prostate 19%, and breast cancer 17%* (statistically non-significant). There is some molecular evidence of this in colon cancer. But not the others....... The catch is that you have to use aspirin adult dose for >5 years. Why? Like most association studies.....No one knows. What good is that?


2. Hormone replacement therapy increases Ovarian cancer incidence This study called the Million Women Study is a large cohort of British women. 948,576 postmenopausal women were assessed for ovarian cancer incidence. Users were 20% more likely to develop Ovarian Cancer. 1 in 5, that seems small, but in a million women (well......just 52k shy) that's alot of cancer!!! Especially such a nasty killer. But here's the kicker....


3. Oral Contraceptive hormones Reduce Colorectal Cancer risk! Wait a second.....Aren't these female hormones too? This study shows an almost 40% reduced incidence of colon cancer in these women from the Women's Health Study. Perhaps this has to do with dosage? But Who Knows....It's an association study!!!


4. Smoking Cuts Risk of Parkinson's Disease So that is what the media says about this study. Ok so now you have got me flipping out. No mechanism, No pathogenesis, No explanation.... Smoking kills, but at least it reduces your likelihood of ALSO having Parkinson's. Almost a 40% reduction in the likelihood of having Parkinson's. How? Who Cares....It's an association study! This kills me. The people could have predisposition genes for nicotine addiction/taste/etc which also have some salutatory effects. I do not think that smoking is what saves these patients brain cells!!!! But that's not what the press will tell you.

The Sherpa Says: What is sold as a good piece of science is quite often a piece of something else! Just because it was toiled over and hard work to develop it was done does not make it true, correct or even appropriate. I am here to say.....If it sounds fishy it probably smells fishy too. Throw out association studies until you have a reason for the association!!!

Menopause, Hormones, and You

In the Wall Street Journal today there is a review article regarding recent literature published on menopausal hormone replacement. This article summarizes the debate regarding hormone therapy but does not get to the meat of an article published in the Journal of the American Medical Association(JAMA). The article has some controversy swriling around it. Mainly, that the p-value (likelihood of chance association) was adjusted after the analysis in response to a JAMA request. This is not usually standard practice for publishers as the p-value is usually accepted at 0.05. In this case it is 0.01. Either way the findings are what is interesting.

Traditionally the thought was that menopause and estrogen deficiency was a disease state. As such the "old time" doctors thought that hormone replacement helped prevent stroke and heart attack risk. This was flipped on its head in 2002 when the WHI released some findings which stated that you are actually at increased risk of heart attack or stroke while on the therapy!
This new study points out that there is a window of new onset menopause where therapy does lower risk, however in the elderly >70 years old there is an increased risk. I think that this study has some merit. However, the results can only be interpreted through a genomic eye. Recently data were released regarding ESR1(estrogen receptor alpha) and increased risk of heart attack in men. Currently there are no definitive data on whether estrogen PLUS some gene polymorphism put you at increased or decreased risk. When that data comes, rest assured that labs will be lining up the postmenopausal women. And when that data comes, you will hear it here First!