title: CYP24A1 and CYP27B1 Polymorphisms, Concentrations of Vitamin D Metabolites, and Odds of Colorectal Adenoma Recurrence.
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 (P(interaction) = 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.
authors.affiliation: a Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine , Nashville , Tennessee , USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Hibler
authors.affiliation: b Mel and Enid Zuckerman College of Public Health, University of Arizona , Tucson , Arizona , USA.
authors.forename: Yann C
authors.initials: YC
authors.lastname: Klimentidis
authors.affiliation: c School of Mathematical and Natural Sciences, Arizona State University , Phoenix , Arizona , USA.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Jurutka
authors.affiliation: b Mel and Enid Zuckerman College of Public Health, University of Arizona , Tucson , Arizona , USA.
authors.forename: Lindsay N
authors.initials: LN
authors.lastname: Kohler
authors.affiliation: d University of Arizona Cancer Center , Tucson , Arizona , USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Lance
authors.affiliation: e Mel and Enid Zuckerman College of Public Health, University of Arizona , Tucson , Arizona , USA and University of Arizona Cancer Center , Tucson , Arizona , USA.
authors.forename: Denise J
authors.initials: DJ
authors.lastname: Roe
authors.affiliation: d University of Arizona Cancer Center , Tucson , Arizona , USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Thompson
authors.affiliation: e Mel and Enid Zuckerman College of Public Health, University of Arizona , Tucson , Arizona , USA and University of Arizona Cancer Center , Tucson , Arizona , USA.
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: Jacobs
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics*; D000236:Adenoma / Q000097:blood / Q000235:genetics* / Q000473:pathology; D000368:Aged; D002112:Calcifediol / Q000097:blood*; D002117:Calcitriol / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics*
chemical_list: C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; C000600378:CYP27B1 protein, human; D002117:Calcitriol; D002112:Calcifediol