CYP24A1 and CYP27B1 Polymorphisms, Concentrations of Vitamin D Metabolites, and Odds of Colorectal Adenoma Recurrence

Elizabeth A. Hibler, Yann C. Klimentidis, Peter W. Jurutka, Lindsay N. Kohler, Peter Lance, Denise J. Roe, Patricia A. Thompson, Elizabeth T. Jacobs

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Development of colorectal adenoma and cancer are associated with low circulating 25-hydroxyvitamin D [25(OH)D] levels. However, less is known regarding colorectal neoplasia risk and variation in CYP27B1 or CYP24A1, genes encoding the enzymes responsible for the synthesis and catabolism of 1α,25-hydroxyvitamin D [1,25(OH)2D]. This study examined associations between CYP27B1 and CYP24A1 polymorphisms, circulating 25(OH)D and 1,25(OH)2D concentrations, and colorectal adenoma recurrence in a pooled sample from 2 clinical trials (n = 1,188). Nominal associations were observed between increasing copies of the T allele in CYP24A1 rs927650 and 25(OH)D concentrations (P = 0.02); as well as colorectal adenoma recurrence, with odds ratios (95% confidence intervals) of 1.30 (0.99-1.70) and 1.38 (1.01-1.89) for heterozygotes and minor allele homozygotes, respectively (P = 0.04). In addition, a statistically significant relationship between CYP24A1 rs35051736, a functional polymorphism, and odds for advanced colorectal adenoma recurrence was observed (P < 0.001). Further, nominally statistically significant interactions were observed between rs2296241 and 25(OH)D as well as rs2762939 and 1,25(OH)2D (Pinteraction = 0.10, respectively). Overall, CYP24A1 polymorphisms may influence the development of advanced lesions, and modify the effect of vitamin D metabolites on adenoma recurrence. Further study is necessary to characterize the differences between circulating vitamin D metabolite measurements compared to cellular level activity in relation to cancer risk.

Original languageEnglish (US)
Pages (from-to)1131-1141
Number of pages11
JournalNutrition and cancer
Volume67
Issue number7
DOIs
StatePublished - Oct 3 2015

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Oncology
  • Nutrition and Dietetics
  • Cancer Research

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