Replication of the 10q11 and Xp11 prostate cancer risk variants: results from a Utah pedigree-based study.

Abstract

A recent genome-wide association study suggested seven new loci as associated with prostate cancer susceptibility. The strongest associated single nucleotide polymorphism (SNP) in each region was identified (rs2660753, rs9364554, rs6465657, rs10993994, rs7931342, rs2735839, rs5945619). We studied these seven SNPs in a replication study consisting of 169 familial prostate cancer cases selected from Utah high-risk prostate cancer pedigrees and 805 controls. We performed subset analyses for aggressive and early-onset prostate cancer. At a nominal significance level, two SNPs were found to be associated with prostate cancer: rs10993994 on chromosome 10q11 [odds ratio (OR), 1.42; 95% confidence interval (95% CI), 1.05-1.90; P = 0.022] and rs5945619 on chromosome Xp11 (OR, 1.54; 95% CI, 1.03-2.31; P = 0.035). Restricting analysis to familial prostate cancer cases with aggressive disease yielded very similar risk estimates at both SNPs. However, subset analysis for familial, early-onset disease indicated highly significant association evidence and substantially higher risk estimates for rs10993994 (OR, 2.20; 95% CI, 1.48-3.27; P < 0.0001). This result suggests that the higher risk estimates from the stage 1 cohort in the original study for rs10993994 may have been due to the early-onset and familial nature of the prostate cancer cases in that cohort. In conclusion, in a small case-control study of prostate cancer cases from Utah high-risk pedigrees, we have significantly replicated association of prostate cancer with rs10993994 (10q11) upon study-wide correction for multiple comparisons. We also nominally replicated the association of prostate cancer with rs5945619 (Xp11). In particular, it seems that the susceptibility locus at 10q11 maybe involved in familial, early-onset disease.