Polymorphisms in the vitamin D receptor gene, ultraviolet radiation, and susceptibility to prostate cancer

• Published in: Environmental and molecular mutagenesis Vol. 43; no. 2; pp. 121 - 127
• Main Authors: Bodiwala, Dhaval, Luscombe, Christopher J., French, Michael E., Liu, Samson, Saxby, Mark F., Jones, Peter W., Fryer, Anthony A., Strange, Richard C.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 2004; Wiley-Liss
• Subjects: Biological and medical sciences; Cell receptors; Cell structures and functions; Disease Susceptibility; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Genotype; Humans; Male; Medical sciences; Miscellaneous; Molecular and cellular biology; Polymorphism, Genetic; prostate cancer; prostate cancer susceptibility; Prostatic Hyperplasia - genetics; Prostatic Neoplasms - genetics; Receptors, Calcitriol - genetics; Risk Factors; Toxicology; ultraviolet radiation; Ultraviolet Rays - adverse effects; vitamin D receptor; Ultraviolet radiation; Toxicology; prostate cancer; Gene; Vitamin D; prostate cancer susceptibility; Genetics; vitamin D receptor; Prostate; Polymorphism; Biological receptor
• ISSN: 0893-6692; 1098-2280
• DOI: 10.1002/em.20000

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, Fok1, and Taq1 sites), haplotypes, and genotype combinations with risk by studying 368 prostate cancer and 243 benign prostatic hypertrophy (BPH) patients. CDX‐2, Fok1, and Taq1 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 Fok1 ff (OR = 2.91) were associated with increased prostate cancer risk. No associations were observed for Taq1 genotypes. Of the genotype combinations, relative to all other CDX‐2 and Taq1 and combinations, GGTT (P = 0.022, OR = 0.30), and relative to all other Fok1 and Taq1 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.