SNPwatch: Prostate Cancer Redux

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.

Following on the heels of last month’s New England Journal of Medicine study on genetic associations with prostate cancer risk are three new papers in Nature Genetics. The new batch not only replicates earlier discoveries but adds at least 16 potential new associations to the mix. While there are too many to list here individually, a few are worthy of particular mention. (Links to 23andMe’s Genome Explorer (now called Browse Raw Data) are provided for each.)

Iceland’s deCODE Genetics compared the genotypes of 10,000 men diagnosed with prostate cancer with those of 29,000 healthy controls. Instead of conducting a genome-wide association study (GWAS) of hundreds of thousands of single nucleotide polymorphisms (SNPs), the authors chose to follow up on two promising candidates identified in previous GWAS. In the current study, both showed associations to prostate cancer risk.

One of the candidates, rs5945572, is located on the X chromosome. Men only have one X chromosome and thus one copy of rs5945572. Those who had the “A” version of the SNP had slightly higher odds of prostate cancer.

The fact that the SNP is located on the X chromosome—which sons inherit only from their mothers—may help to explain why brothers of men with prostate cancer are at greater risk of being affected than fathers are. If a father has the protective “G” version of the SNP on his X chromosome, he cannot pass it on to his sons; the contribution of this SNP to a man’s risk of prostate cancer is determined by which version his mother passes to him.

The second SNP identified in the deCODE study was rs721048, on chromosome 2. This SNP was analagous to rs2710646, which is in 23andMe’s Genome Explorer (Browse Raw Data). Each copy of the “A” version of rs2710646 slightly raised men’s odds of prostate cancer.

The other two studies each examined 5,000 cases and 5,000 controls. While the studies found a number of significant associations, both independently identified a link between rs10993994 and prostate cancer risk. Each copy of the “T” version of rs10993994 raised men’s odds of prostate cancer. This SNP is located in a gene called MSMB, which encodes a prostate-specific protein thought to be a biomarker for advanced forms of prostate cancer. The authors speculate that the different versions of this SNP might affect levels of the MSMB protein, but this will have to be shown in future experiments.

Further replication studies will have to be performed before all of these associations are fully accepted by the scientific community. But because rs10993994 has already been identified in two large studies, we’ll get it into the Gene Journal article (now called Health and Traits) on prostate cancer as soon as possible. Check back soon to see how this SNP fits into the picture!

(2/12/08 update: added PubMed links to study abstracts. -Andro Hsu)


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