TY - JOUR
T1 - Genetic variation in vitamin D-related genes and risk of colorectal cancer in African Americans
AU - Pibiri, Fabio
AU - Kittles, Rick A.
AU - Sandler, Robert S.
AU - Keku, Temitope O.
AU - Kupfer, Sonia S.
AU - Xicola, Rosa M.
AU - Llor, Xavier
AU - Ellis, Nathan A.
N1 - Funding Information:
Acknowledgments The authors are grateful to Sariya Siddiqi for assistance with DNA preparation, Ebony Shah for advice on the iPLEX reactions, Archana Krishnan for helping in DNA extraction, and the Core Genomics Facility for assistance with Sequenom genotyping. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Numbers R01CA140804, K08CA142892, U01CA153060 and by grants from the American Institute for Cancer Research and the American Cancer Society, Illinois Division. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the other sponsors.
PY - 2014/5
Y1 - 2014/5
N2 - 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.
AB - 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.
KW - African American population
KW - Cancer health disparities
KW - Colorectal cancer
KW - Genetic risk factors
KW - Vitamin D
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U2 - 10.1007/s10552-014-0361-y
DO - 10.1007/s10552-014-0361-y
M3 - Article
C2 - 24562971
AN - SCOPUS:84898864517
SN - 0957-5243
VL - 25
SP - 561
EP - 570
JO - Cancer Causes and Control
JF - Cancer Causes and Control
IS - 5
ER -