Genetic associations in the vitamin D receptor and colorectal cancer in African Americans and Caucasians.

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...

Full description

Bibliographic Details
Main Authors: Sonia S Kupfer, Jeffrey R Anderson, Anton E Ludvik, Stanley Hooker, Andrew Skol, Rick A Kittles, Temitope O Keku, Robert S Sandler, Clara Ruiz-Ponte, Sergi Castellvi-Bel, Antoni Castells, Angel Carracedo, Nathan A Ellis
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3203108?pdf=render
_version_ 1818040808184479744
author Sonia S Kupfer
Jeffrey R Anderson
Anton E Ludvik
Stanley Hooker
Andrew Skol
Rick A Kittles
Temitope O Keku
Robert S Sandler
Clara Ruiz-Ponte
Sergi Castellvi-Bel
Antoni Castells
Angel Carracedo
Nathan A Ellis
author_facet Sonia S Kupfer
Jeffrey R Anderson
Anton E Ludvik
Stanley Hooker
Andrew Skol
Rick A Kittles
Temitope O Keku
Robert S Sandler
Clara Ruiz-Ponte
Sergi Castellvi-Bel
Antoni Castells
Angel Carracedo
Nathan A Ellis
author_sort Sonia S Kupfer
collection DOAJ
description 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.
first_indexed 2024-12-10T08:20:24Z
format Article
id doaj.art-a898174f74924e6b963aba7088de43c7
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-12-10T08:20:24Z
publishDate 2011-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-a898174f74924e6b963aba7088de43c72022-12-22T01:56:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01610e2612310.1371/journal.pone.0026123Genetic associations in the vitamin D receptor and colorectal cancer in African Americans and Caucasians.Sonia S KupferJeffrey R AndersonAnton E LudvikStanley HookerAndrew SkolRick A KittlesTemitope O KekuRobert S SandlerClara Ruiz-PonteSergi Castellvi-BelAntoni CastellsAngel CarracedoNathan A EllisLow 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.http://europepmc.org/articles/PMC3203108?pdf=render
spellingShingle Sonia S Kupfer
Jeffrey R Anderson
Anton E Ludvik
Stanley Hooker
Andrew Skol
Rick A Kittles
Temitope O Keku
Robert S Sandler
Clara Ruiz-Ponte
Sergi Castellvi-Bel
Antoni Castells
Angel Carracedo
Nathan A Ellis
Genetic associations in the vitamin D receptor and colorectal cancer in African Americans and Caucasians.
PLoS ONE
title Genetic associations in the vitamin D receptor and colorectal cancer in African Americans and Caucasians.
title_full Genetic associations in the vitamin D receptor and colorectal cancer in African Americans and Caucasians.
title_fullStr Genetic associations in the vitamin D receptor and colorectal cancer in African Americans and Caucasians.
title_full_unstemmed Genetic associations in the vitamin D receptor and colorectal cancer in African Americans and Caucasians.
title_short Genetic associations in the vitamin D receptor and colorectal cancer in African Americans and Caucasians.
title_sort genetic associations in the vitamin d receptor and colorectal cancer in african americans and caucasians
url http://europepmc.org/articles/PMC3203108?pdf=render
work_keys_str_mv AT soniaskupfer geneticassociationsinthevitamindreceptorandcolorectalcancerinafricanamericansandcaucasians
AT jeffreyranderson geneticassociationsinthevitamindreceptorandcolorectalcancerinafricanamericansandcaucasians
AT antoneludvik geneticassociationsinthevitamindreceptorandcolorectalcancerinafricanamericansandcaucasians
AT stanleyhooker geneticassociationsinthevitamindreceptorandcolorectalcancerinafricanamericansandcaucasians
AT andrewskol geneticassociationsinthevitamindreceptorandcolorectalcancerinafricanamericansandcaucasians
AT rickakittles geneticassociationsinthevitamindreceptorandcolorectalcancerinafricanamericansandcaucasians
AT temitopeokeku geneticassociationsinthevitamindreceptorandcolorectalcancerinafricanamericansandcaucasians
AT robertssandler geneticassociationsinthevitamindreceptorandcolorectalcancerinafricanamericansandcaucasians
AT clararuizponte geneticassociationsinthevitamindreceptorandcolorectalcancerinafricanamericansandcaucasians
AT sergicastellvibel geneticassociationsinthevitamindreceptorandcolorectalcancerinafricanamericansandcaucasians
AT antonicastells geneticassociationsinthevitamindreceptorandcolorectalcancerinafricanamericansandcaucasians
AT angelcarracedo geneticassociationsinthevitamindreceptorandcolorectalcancerinafricanamericansandcaucasians
AT nathanaellis geneticassociationsinthevitamindreceptorandcolorectalcancerinafricanamericansandcaucasians