Prostate cancer susceptibility is mediated by interactions between exposure to ultraviolet radiation and polymorphisms in the 5' haplotype block of the vitamin D receptor gene.

Abstract Vitamin D receptor (VDR) polymorphisms are prostate cancer risk candidates. We determined if SNPs in haplotype block sub-regions C2 (SNPs C2-1, G/C 3436 , C2-2, A/G 3944 ) or C1 (C1-1, C/T 20965 , C1-2, C/T 30056 ) are associated with risk in an ultraviolet radiation (UVR)-dependent manner. In men with very low exposure, SNPs in both sub-regions were associated with risk. Various haplotypes in haplotype block C including G 3436 -A 3944 -C 20965 -C 30056 , (G or C)-A-C-C and G-A-(C or T)-C were significantly associated with increased risk (odds ratios between 1.95 and 2.37). These findings suggest various block C SNPs are associated with prostate cancer risk via a mechanism involving exposure to sunlight.