title: Associations between G/A1229, A/G3944, T/C30875, C/T48200 and C/T65013 genotypes and haplotypes in the vitamin D receptor gene, ultraviolet radiation and susceptibility to prostate cancer.
abstract: 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.
authors.affiliation: Human Genomics Research Group, Institute of Science and Technology in Medicine, Keele University Medical School, Hartshill Campus, University Hospital of North Staffordshire, Staffordshire, England.
authors.forename: Sam
authors.initials: S
authors.lastname: Moon
authors.forename: Sarah
authors.initials: S
authors.lastname: Holley
authors.forename: Dhaval
authors.initials: D
authors.lastname: Bodiwala
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Luscombe
authors.forename: Michael E
authors.initials: ME
authors.lastname: French
authors.forename: Samson
authors.initials: S
authors.lastname: Liu
authors.forename: Mark F
authors.initials: MF
authors.lastname: Saxby
authors.forename: Peter W
authors.initials: PW
authors.lastname: Jones
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Fryer
authors.forename: Richard C
authors.initials: RC
authors.lastname: Strange
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000235:genetics*; D014466:Ultraviolet Rays
chemical_list: D017931:DNA Primers; D018167:Receptors, Calcitriol