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Cancer Causes & Control
Published in: Cancer Causes & Control 5/2014

Open Access 01-05-2014 | Original paper

Genetic variation in vitamin D-related genes and risk of colorectal cancer in African Americans

Authors: Fabio Pibiri, Rick A. Kittles, Robert S. Sandler, Temitope O. Keku, Sonia S. Kupfer, Rosa M. Xicola, Xavier Llor, Nathan A. Ellis

Published in: Cancer Causes & Control | Issue 5/2014

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Abstract

Purpose

Disparities in both colorectal cancer (CRC) incidence and survival impact African Americans (AAs) more than other US ethnic groups. Because vitamin D is thought to protect against CRC and AAs have lower serum vitamin D levels, genetic variants that modulate the levels of active hormone in the tissues could explain some of the cancer health disparity. Consequently, we hypothesized that genetic variants in vitamin D-related genes are associated with CRC risk.

Methods

To test this hypothesis, we studied 39 potentially functional single-nucleotide polymorphisms (SNPs) in eight genes (CYP2R1, CYP3A4, CYP24A1, CYP27A1, CYP27B1, GC, DHCR7, and VDR) in 961 AA CRC cases and 838 healthy AA controls from Chicago and North Carolina. We tested whether SNPs are associated with CRC incidence using logistic regression models to calculate p values, odds ratios, and 95 % confidence intervals. In the logistic regression, we used a log-additive genetic model and used age, gender, and percent West African ancestry, which we estimated with the program STRUCTURE, as covariates in the models.

Results

A nominally significant association was detected between CRC and the SNP rs12794714 in the vitamin D 25-hydroxylase gene CYP2R1 (p = 0.019), a SNP that has previously been associated with serum vitamin D levels. Two SNPs, rs16847024 in the GC gene and rs6022990 in the CYP24A1 gene, were nominally associated with left-sided CRC (p = 0.015 and p = 0.018, respectively).

Conclusions

Our results strongly suggest that genetic variation in vitamin D-related genes could affect CRC susceptibility in AAs.
Appendix
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Metadata
Title
Genetic variation in vitamin D-related genes and risk of colorectal cancer in African Americans
Authors
Fabio Pibiri
Rick A. Kittles
Robert S. Sandler
Temitope O. Keku
Sonia S. Kupfer
Rosa M. Xicola
Xavier Llor
Nathan A. Ellis
Publication date
01-05-2014
Publisher
Springer International Publishing
Published in
Cancer Causes & Control / Issue 5/2014
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI
https://doi.org/10.1007/s10552-014-0361-y

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