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Genetic Associations in the Vitamin D Receptor and Colorectal Cancer in African Americans and Caucasians

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Title: Genetic Associations in the Vitamin D Receptor and Colorectal Cancer in African Americans and Caucasians
Author(s): Kupfer, Sonia S.; Anderson, Jeffrey R.; Ludvik, Anton E.; Hooker, Stanley; Skol, Andrew; Kittles, Rick A.; Keku, Temitope O.; Sandler, Robert S.; Ruiz-Ponte, Clara; Castellvi-Bel, Sergi; Castells, Antoni; Carracedo, Angel; Ellis, Nathan A.
Abstract: Low vitamin D levels are associated with an increased incidence of colorectal cancer (CRC) and higher mortality from the disease. In the US, African Americans (AAs) have the highest CRC incidence and mortality and the lowest levels of vitamin D. Single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene have been previously associated with CRC, but few studies have included AAs. We studied 795 AA CRC cases and 985 AA controls from Chicago and North Carolina as well as 1324 Caucasian cases and 990 Caucasian controls from Chicago and Spain. We genotyped 54 tagSNPs in VDR (46586959 to 46521297 Mb) and tested for association adjusting for West African ancestry, age, gender, and multiple testing. Untyped markers were imputed using MACH1.0. We analyzed associations by gender and anatomic location in the whole study group as well as by vitamin D intake in the North Carolina AA group. In the joint analysis, none of the SNPs tested was significantly associated with CRC. For four previously tested restriction fragment length polymorphisms, only one (referred to as ApaI), tagged by the SNP rs79628898, had a nominally significant p-value in AAs; none of these polymorphisms were associated with CRC in Caucasians. In the North Carolina AAs, for whom we had vitamin D intake data, we found a significant association between an intronic SNP rs11574041 and vitamin D intake, which is evidence for a VDR gene-environment interaction in AAs. In summary, using a systematic tagSNP approach, we have not found evidence for significant associations between VDR and CRC in AAs or Caucasians.
Issue Date: 2011-10-27
Publisher: Public Library of Science
Citation Info: Kupfer SS, Anderson JR, Ludvik AE, Hooker S, Skol A, et al. 2011. Genetic Associations in the Vitamin D Receptor and Colorectal Cancer in African Americans and Caucasians. PLoS ONE 6(10): e26123. doi:10.1371/journal.pone.0026123
Type: Article
Description: © 2011 Kupfer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. doi:10.1371/journal.pone.0026123
URI: http://hdl.handle.net/10027/8548
ISSN: 1932-6203
Sponsor: This work was supported by research grants from the National Institutes of Health (K08 CA142892 to S.S.K.; R01 CA 66635 to R.S.S.; and U01 CA153060 to N.A.E.), American Institute for Cancer Research (09-A116 to N.A.E.), and American Cancer Society Illinois Division (PSB 09-02 to N.A.E.). Institutional support was provided by the Digestive Disease Research Core Centers at UC and UNC (P30 DK42086 and P30 DK34987, respectively), The Cancer Research Foundation, the University of Chicago Comprehensive Cancer Research Center, development grants from the American Cancer Society Institutional Research Grant program and the Clinical Translational Science Award, and support from the Department of Medicine at the University of Chicago. The authors’ Spanish partners were supported by Xunta de Galicia (PGIDIT 08CSA005208PR to A. Carracedo), ISCIII-Subdireccio´n General de Evaluacio´n y Fomento de la Investigacio´n/FEDER (08/ 0024, 08/1276, PS09/02368 to A. Carracedo), Instituto de Salud Carlos III (Accio´n Transversal de Ca´ncer), Ministerio de Ciencia e Innovacio´n (SAF2010-19273), Asociacio´n Espan˜ ola contra el Ca´ncer (Fundacio´n Cientı´fica y Junta de Barcelona), Fundacio´ Olga Torres (to S.C.-B. and C.R.-P.), and FP7 CHIBCHA Consortium (A. Carracedo and S.C.B.). S.C.-B. is supported by a contract from the Fondo de Investigacio´n Sanitaria (CP 03-0070). CIBERehd and CIBERER are funded by the Instituto de Salud Carlos III. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Date Available in INDIGO: 2012-08-18
 

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