Vitamin D Receptor Gene Polymorphism and the Risk of Colorectal Cancer: A Nested Case-Control Study

PLoS One. 2016 Oct 13;11(10):e0164648. doi: 10.1371/journal.pone.0164648. eCollection 2016.

Abstract

Epidemiological and experimental evidence suggest that vitamin D is protective against the risk of colorectal cancer. Polymorphisms in the gene encoding vitamin D receptor (VDR), which mediates most of the known cellular effects of vitamin D, have been suggested to alter this association. Here, using a tag SNP approach, we comprehensively evaluated the role of common genetic variants in VDR and their interaction with plasma vitamin D levels in relation to colorectal cancer risk in Japanese populations. A total of 356 colorectal cancer cases and 709 matched control subjects were selected from the participants of the Japan Public Health Center-based Prospective Cohort Study. Among these subjects, 29 VDR single nucleotide polymorphisms (SNPs) were selected and genotyped, and plasma vitamin D concentrations were measured. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of colorectal cancer, with adjustment for potential confounding factors. Among the results, eight VDR SNPs, namely rs2254210, rs1540339, rs2107301, rs11168267, rs11574113, rs731236, rs3847987 and rs11574143, the latter 5 of which were located in the 3' region, were nominally associated with the risk of colorectal cancer (P = 0.01-0.048). Furthermore, of the above 5 3' region SNPs, the inverse associations for 3 SNPs (rs11574113, rs3847987 and rs11574143) appeared to be evident only in those with high plasma vitamin D concentration. However, neither of these direct and suggestive interaction analysis associations was significant after multiple testing adjustment. Overall, the findings of this study provide only limited support for an association between common genetic variations in VDR and colorectal cancer risk in the Japanese population.

MeSH terms

  • 3' Untranslated Regions
  • Adult
  • Aged
  • Alleles
  • Asian Continental Ancestry Group / genetics
  • Case-Control Studies
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Female
  • Genotype
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Receptors, Calcitriol / genetics*
  • Risk Factors

Substances

  • 3' Untranslated Regions
  • Receptors, Calcitriol

Grant support

This study was supported by a National Cancer Center Research and Development Fund (23-A-31[toku] and 26-A-2 since 2011), a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan (from 1989 to 2010), Funds for the Integrated Promotion of Social System Reform and Research and Development (37201101-01 from 2011 to 2013) from the Japan Science and Technology Agency, the Practical Research for Innovative Cancer Control (15Ack0106095h0002 since 2015) from the Japan Agency for Medical Research and Development, and a Grant-in-Aid for Scientific Research C (15K08722 since 2015) from the Japan Society for the Promotion of Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.