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

Cancer. 2015 Jun 15;121(12):1949-56. doi: 10.1002/cncr.29320. Epub 2015 Mar 2.


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.

Keywords: circulating 25-hydroxyvitamin D; fatal prostate cancer; gene-environment interaction; single-nucleotide polymorphisms; vitamin D genes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Cell Line, Tumor
  • Cohort Studies
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genotype
  • Humans
  • Male
  • National Cancer Institute (U.S.)
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Prostatic Neoplasms / blood*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / mortality
  • Risk Factors
  • Treatment Outcome
  • United States / epidemiology
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D / genetics


  • Vitamin D
  • 25-hydroxyvitamin D