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, Michael P Lance, Denise Roe, Patricia A. Thompson, Elizabeth T Jacobs

Research output: Contribution to journalArticle

10 Citations (Scopus)

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

Fingerprint

25-Hydroxyvitamin D3 1-alpha-Hydroxylase
Vitamin D
Adenoma
Recurrence
Alleles
Homozygote
Heterozygote
Colorectal Neoplasms
Neoplasms
Odds Ratio
Vitamin D3 24-Hydroxylase
Clinical Trials
Confidence Intervals
Enzymes
Genes

ASJC Scopus subject areas

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

Cite this

CYP24A1 and CYP27B1 Polymorphisms, Concentrations of Vitamin D Metabolites, and Odds of Colorectal Adenoma Recurrence. / Hibler, Elizabeth A.; Klimentidis, Yann C; Jurutka, Peter W.; Kohler, Lindsay N.; Lance, Michael P; Roe, Denise; Thompson, Patricia A.; Jacobs, Elizabeth T.

In: Nutrition and Cancer, Vol. 67, No. 7, 03.10.2015, p. 1131-1141.

Research output: Contribution to journalArticle

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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.",
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AU - Jacobs, Elizabeth T

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AB - 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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