Associations of vitamin D pathway genes with circulating 25-hydroxyvitamin-D, 1,25-dihydroxyvitamin-D, and prostate cancer: a nested case-control study
Author(s)
Type
Journal Article
Abstract
PURPOSE: Vitamin D pathway single nucleotide polymorphisms (SNPs) are potentially useful proxies for investigating whether circulating vitamin D metabolites [total 25-hydroxyvitamin-D, 25(OH)D; 1,25-dihydroxyvitamin, 1,25(OH)2D] are causally related to prostate cancer. We investigated associations of sixteen SNPs across seven genes with prostate-specific antigen-detected prostate cancer. METHODS: In a nested case-control study (within the ProtecT trial), we estimated odds ratios and 95 % confidence intervals (CIs) quantifying associations between SNPs and prostate cancer. Subgroup analyses investigated whether associations were stronger in men who had high/low sun exposure [a proxy for 25(OH)D]. We quantified associations of SNPs with stage (T1-T2/T3-T4) and grade (<7/≥7). Multiple variant scores included SNPs encoding proteins involved in 25(OH)D synthesis and metabolism. RESULTS: We included 1,275 prostate cancer cases (141 locally advanced, 385 high grades) and 2,062 healthy controls. Vitamin D-binding protein SNPs were associated with prostate cancer (rs4588-A: OR 1.20, CI 1.01, 1.41, p = 0.04; rs7041-T: OR 1.19, CI 1.02, 1.38, p = 0.03). Low 25(OH)D metabolism score was associated with high (vs low) grade (OR 0.76, CI 0.63, 0.93, p = 0.01); there was a similar association of its component variants: rs6013897-A in CYP24A1 (OR 0.78, CI 0.60, 1.01, p = 0.06) and rs10877012-T in CYP27B1 (OR 0.80, CI 0.63, 1.02, p = 0.07). There was no evidence that associations differed by level of sun exposure. CONCLUSION: We found some evidence that vitamin D pathway SNPs were associated with prostate cancer risk and grade, but not stage. There was no evidence of an association in men with deficient vitamin D (measured by having low sun exposure).
Date Issued
2014-12-09
Date Acceptance
2014-11-13
Citation
Cancer Causes & Control, 2014, 26 (2), pp.205-218
ISSN
1573-7225
Publisher
Springer Verlag
Start Page
205
End Page
218
Journal / Book Title
Cancer Causes & Control
Volume
26
Issue
2
Copyright Statement
This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
License URL
Subjects
25-Hydroxyvitamin D3 1-alpha-Hydroxylase
Aged
Alleles
Biomarkers, Tumor
Calcitriol
Case-Control Studies
Gene-Environment Interaction
Humans
Male
Middle Aged
Odds Ratio
Polymorphism, Single Nucleotide
Prostate-Specific Antigen
Prostatic Neoplasms
Risk
Risk Assessment
Risk Factors
Vitamin D
Vitamin D-Binding Protein
Vitamin D3 24-Hydroxylase
1,25-dihydroxyvitamin-D
25 hydroxyvitamin-D
Prostate cancer
Vitamin D pathway genes
Epidemiology
1117 Public Health And Health Services
1112 Oncology And Carcinogenesis
Publication Status
Published