Genetic variants in the vitamin D receptor gene and prostate cancer risk

Vitamin D receptor (VDR), a member of the steroid/thyroid hormone nuclear receptor family, is bound by the steroid hormone 1,25-dihydroxyvitamin D-3, which is thought to play a role in the etiology and progression of prostate cancer. Polymorphisms in the VDR gene have been associated with prostate cancer risk, although findings are inconclusive. The purpose of this study was to determine if VDR polymorphisms were associated with prostate cancer risk using a large, Australian population-based study of 812 cases and 713 controls frequency-matched by age. As the 3' region polymorphisms are in strong linkage disequilibrium, for joint effects, we only evaluated the common g.60890G > A polymorphism with the unlinked g.27823C > T (5' region) polymorphism. Allele frequencies were similar in cases and controls (g.27823C > T, 36% versus 36%; g.60890 G > A, 41% versus 43%). No genotypes were individually associated with prostate cancer risk (all P > 0.3). All nine possible genotype combinations were evident, and although the g.27823CT/g.60890GA combination was nominally more prevalent in controls (24%) than in cases (19%, P = 0.03), there was no difference in the combined genotype distribution between cases and controls (P = 0.2). The associations of risk with genotype were between 0.91 and 1.03, all with 95% confidence intervals within 0.81 to 1.15. In conclusion, VDR polymorphisms either alone or in combination do not seem to contribute appreciably to prostate cancer risk.