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Colon cancer 30 percent more likely if problems with Vitamin D genes CYP24A1 or CYP27B1 – Nov 2015

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

Nutrition and Cancer, Volume 67, Issue 7, 2015, DOI:10.1080/01635581.2015.1068818
Elizabeth A. Hiblera, Yann C. Klimentidisb, Peter W. Jurutkac, Lindsay N. Kohlerb, Peter Lanced, Denise J. Roee, Patricia A. Thompsond & Elizabeth T. Jacobse*

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.

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