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Associations Between G/A 1229 , A/G 3944 , T/C 30875 , C/T 48200 and C/T 65013 Genotypes and Haplotypes in the Vitamin D Receptor Gene, Ultraviolet Radiation and Susceptibility to Prostate Cancer
Author(s) -
Moon Sam,
Holley Sarah,
Bodiwala Dhaval,
Luscombe Christopher J.,
French Michael E.,
Liu Samson,
Saxby Mark F.,
Jones Peter W.,
Fryer Anthony A.,
Strange Richard C.
Publication year - 2006
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/j.1529-8817.2005.00219.x
Subject(s) - single nucleotide polymorphism , linkage disequilibrium , odds ratio , snp , haplotype , prostate cancer , calcitriol receptor , genotype , genetics , biology , tag snp , allele , cancer , medicine , oncology , gene
Summary Ultraviolet radiation (UVR) may protect against prostate cancer via a mechanism involving vitamin D. Thus, the vitamin D receptor ( VDR ) gene is a susceptibility candidate, though published data are discrepant. We studied the association of prostate cancer risk with five VDR single nucleotide polymorphisms (SNPs): G/A 1229 (SNP 1), A/G 3944 (SNP 2), T/C 30875 (SNP 3), C/T 48200 (SNP 4) and C/T 65013 (SNP 5), in 430 cancer and 310 benign prostatic hypertrophy (BPH) patients. The SNP 2 GG genotype frequency was lower in cancer than BPH patients (odds ratio = 0.63, 95% CI = 0.41–0.98, p = 0.039). SNPs 1 and 2, and SNPs 4 and 5, were in linkage disequilibrium. Two copies of haplotypes comprising SNPs 1‐2, G‐G (odds ratio = 0.63, p = 0.039), SNPs 2‐3 G‐C (odds ratio = 0.45, p = 0.008) and SNPs 1‐2‐3 G‐G‐C (odds ratio = 0.44, p = 0.006), but not SNPs 1‐3, G‐C (odds ratio = 0.81, p = 0.34), were associated with reduced risk (reference, no copies of the haplotypes) . These associations were observed after stratification of subjects by extent of UVR exposure. These data show that SNP 2 GG genotype mediates prostate cancer risk, complementing studies reporting this allele is protective in malignant melanoma pathogenesis. They further suggest that published associations of risk with SNP 1 may result from linkage disequilibrium with SNP 2.