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Polymorphisms in the vitamin D receptor gene, ultraviolet radiation, and susceptibility to prostate cancer
Author(s) -
Bodiwala Dhaval,
Luscombe Christopher J.,
French Michael E.,
Liu Samson,
Saxby Mark F.,
Jones Peter W.,
Fryer Anthony A.,
Strange Richard C.
Publication year - 2004
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.20000
Subject(s) - calcitriol receptor , prostate cancer , genotype , odds ratio , vitamin d and neurology , haplotype , medicine , cancer , biology , oncology , physiology , endocrinology , genetics , gene
Ultraviolet radiation (UVR) exposure may protect against prostate cancer development via a mechanism involving vitamin D. The vitamin D receptor ( VDR ) gene is therefore a candidate susceptibility factor for prostate cancer. This possibility has been previously investigated with conflicting results. We examined the association of VDR genotypes (variants at the CDX‐2 , Fok 1, and Taq 1 sites), haplotypes, and genotype combinations with risk by studying 368 prostate cancer and 243 benign prostatic hypertrophy (BPH) patients. CDX‐2 , Fok 1, and Taq 1 genotype and haplotype frequencies were not significantly different in cancer and BPH patients. As the impact of VDR polymorphisms may depend on UVR exposure, we studied associations of variants with risk in men stratified into low (below median) and high (above median) cumulative exposure/year groups. In men with UVR exposure above the median (1,100 hr/year), CDX‐2 GA and AA (odds ratios [OR] = 2.11 and 2.02, respectively) and Fok 1 ff (OR = 2.91) were associated with increased prostate cancer risk. No associations were observed for Taq 1 genotypes. Of the genotype combinations, relative to all other CDX‐2 and Taq 1 and combinations, GGTT ( P = 0.022, OR = 0.30), and relative to all other Fok 1 and Taq 1 combinations, FFTT ( P = 0.026, OR = 0.35) were associated with reduced prostate cancer risk in the presence of the main effects. None of the other two‐ or three‐genotype combinations was associated with risk. These data indicate that VDR variants influence prostate cancer risk and that this association is dependent on the extent of UVR exposure. Environ. Mol. Mutagen. 43:121–127, 2004. © 2004 Wiley‐Liss, Inc.