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

Vitamin D receptor (VDR) polymorphisms are prostate cancer risk candidates. We determined if SNPs in haplotype block sub-regions C2 (SNPs C2-1, G/C3436, C2-2, A/G3944) or C1 (C1-1, C/T20965, C1-2, C/T30056) 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 G3436-A3944-C20965-C30056, (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.