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- Title
Circulating vitamin D, vitamin D-related genetic variation, and risk of fatal prostate cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium.
- Authors
Shui, Irene M.; Mondul, Alison M.; Lindström, Sara; Tsilidis, Konstantinos K.; Travis, Ruth C.; Gerke, Travis; Albanes, Demetrius; Mucci, Lorelei A.; Giovannucci, Edward; Kraft, Peter
- Abstract
BACKGROUND Evidence from experimental animal and cell line studies supports a beneficial role for vitamin D in prostate cancer (PCa). Although the results from human studies have been mainly null for overall PCa risk, there may be a benefit for survival. This study assessed the associations of circulating 25-hydroxyvitamin D (25(OH)D) and common variations in key vitamin D-related genes with fatal PCa. METHODS In a large cohort consortium, 518 fatal cases and 2986 controls with 25(OH)D data were identified. Genotyping information for 91 single-nucleotide polymorphisms (SNPs) in 7 vitamin D-related genes (vitamin D receptor, group-specific component, cytochrome P450 27A1 [ CYP27A1], CYP27B1, CYP24A1, CYP2R1, and retinoid X receptor α) was available for 496 fatal cases and 3577 controls. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations of 25(OH)D and SNPs with fatal PCa. The study also tested for 25(OH)D-SNP interactions among 264 fatal cases and 1169 controls. RESULTS No statistically significant relationship was observed between 25(OH)D and fatal PCa (OR for extreme quartiles, 0.86; 95% CI, 0.65-1.14; P for trend = .22) or the main effects of the SNPs and fatal PCa. There was evidence suggesting that associations of several SNPs, including 5 related to circulating 25(OH)D, with fatal PCa were modified by 25(OH)D. Individually, these associations did not remain significant after multiple testing; however, the P value for the set-based test for CYP2R1 was .002. CONCLUSIONS Statistically significant associations were not observed for either 25(OH)D or vitamin D-related SNPs with fatal PCa. The effect modification of 25(OH)D associations by biologically plausible genetic variation may deserve further exploration. Cancer 2015;121:1949-1956. © 2015 American Cancer Society.
- Subjects
PROSTATE cancer risk factors; NATIONAL Cancer Institute (U.S.); THERAPEUTIC use of vitamin D; PROSTATE cancer &; genetics; GENOTYPE-environment interaction; BREAST cancer treatment; SINGLE nucleotide polymorphisms
- Publication
Cancer (0008543X), 2015, Vol 121, Issue 12, p1949
- ISSN
0008-543X
- Publication type
Article
- DOI
10.1002/cncr.29320