In a paper published today, a team of scientists from deCODE genetics (Nasdaq:DCGN) and academic colleagues from Europe and the United States report the discovery of two single letter variations (SNPs) on chromosome 17 associated with increased risk of prostate cancer. Intriguingly, one of the variants is also associated with decrease in risk of type 2 diabetes (T2D). The increase in risk of prostate cancer conferred by these variants is relatively modest: between 20 and 30% per copy carried compared to individuals without the variants.
But because these variants are very common, they are estimated to play a role in more than a third of prostate cancer cases. The study included some 3,500 prostate cancer patients and more than 14,000 controls from Iceland, Spain, the Netherlands and the U.S. The paper, entitled “Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes,” is published online today Nature Genetics at www.nature.com/ng and is scheduled to appear in the August print edition of the journal.
Adding these new variants to those previously discovered by deCODE on chromosome 8q24, the company now has a collection of genetic factors with sufficient impact on individual risk of prostate cancer to develop a DNA-based risk screening test. Such a test could be used to identify individuals who should receive frequent screening.
deCODE has recently published the identification of two variants on chromosome 8q24 linked to increased risk of prostate cancer, the only two variants to emerge with genome-wide significance from the first-pass analysis of more than 300,000 SNPs captured by the Illumina Hap300 bead arrays. However it was clear that major variants influencing the risk of prostate cancer remained unidentified, so the deCODE team followed up on previously reported family-based linkage signals on the long arm of chromosome 17. By genotyping additional markers in this region in case-control cohorts from Iceland, Spain, the Netherlands and the U.S., the deCODE team discovered and replicated two new SNPs conferring risk of prostate cancer: rs4430796 within the TCF2 gene on chromosome 17q12 previously identified as a candidate gene in T2D; and rs1859962 on 17q24.
Previous epidemiological studies have uncovered an inverse relationship between the incidence of prostate cancer and type 2 diabetes (T2D). The deCODE team therefore decided to investigate whether the risk variant in the TCF2 gene might correlate with decreased likelihood of T2D. In a case-control T2D cohort in Iceland, the risk allele of rs4430796 was found to confer an approximately 10% decrease in the likelihood of T2D, a result that was confirmed in seven additional case control T2D cohorts in individuals of European, African and Asian ancestry.