SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason, it is important to remember that the studies we describe in SNPwatch are for informational and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.A new study in the New England Journal of Medicine illustrates how a few locations in the human genome that are weakly associated with a disease seem to work together to produce a much more dramatic effect once combined.The study concentrated on five particular points in the genome that have been shown to influence a man’s chances of developing prostate cancer, depending on which letter of the DNA code – A, T, G or C – he has at that point in his genome. Scientists refer to these one-letter variations as single-nucleotide polymorphisms, or SNPs.Individually, none of the five SNPs in the NEJM study affects a man’s chances of developing prostate cancer very much. But when researchers compared 2,893 Swedish men with prostate cancer to 1,781 control subjects who were free of the disease, they found that a man’s overall genotype at those five SNPs was strongly correlated with which group he fell into. The study found that those five SNPs alone could account for 40% of the prostate cancers in the study population. Having a more prostate cancer-prone version at four of the locations plus a family history of prostate cancer, or having a more cancer-prone version at all five SNPs and no family history, increased a man’s chances of having the disease by nearly 10-fold.In a New York Times story about the NEJM paper, one of its authors suggested that men who find they have an elevated genetic risk based on the five SNPs might want to start getting screened for prostate cancer at 35 rather than the currently recommended age of 50.23andMe can’t comment on that recommendation, for a number of reasons. One of them is the fact that things like diet, environment, lifetyle and just plain luck are at least as important as genetics in determining whether a man will develop prostate cancer. More than half of the men in the NEJM study who did not have the disease still had the cancer-prone version at two or more SNPs. And one-third of the men with prostate cancer had zero or only one cancer-prone SNP.23andMe customers can determine their own genotypes at all five SNPs identified in the NEJM paper. Two of them – rs6983267 and rs1447295 – are in the prostate cancer Gene Journal (now called Health and Traits) entry. In the NEJM study and several others that have been done to date, researchers have found that men with prostate cancer are more likely to have at least one “G” at rs6983267. At rs1447295, they are more likely to have at least one “A.”Another two of the five SNPs – rs4430796 and rs1859962 – appear in our Genome Explorer (now called Browse Raw Data). Men in the NEJM study found that having two “A”s at rs4430796 were more likely to have prostate cancer, as were men with two “G”s at rs1859962.And our customers can determine their genotype at the fifth location by using the Genome Explorer (Browse Raw Data) to look at a nearby SNP, rs10505483. In the NEJM study, men who had at least one “T” in that location were more likely to have prostate cancer (note however, that the researchers actually looked at a different but closely linked SNP, rs16901979).The table below shows the individual effects of the five SNPs. The column labeled “Effect”shows how much more likely a person with the high-risk version in the study was to have prostate cancer compared to someone with the low-risk version.The table clearly shows that none of the five SNPs has a dramatic effect by itself. But when combined, even minor elevations in risk can have a major effect.At this point, nobody should gauge their chances of developing prostate cancer based on genetic information. But the NEJM paper and other recent developments suggest genetic information may eventually help guide physicians in the diagnosis and treatment of the disease.
SNPwatch: Prostate Cancer
January 17, 2008