Premium
Novel colon cancer susceptibility variants identified from a genome‐wide association study in African Americans
Author(s) -
Wang Hansong,
Schmit Stephanie L.,
Haiman Christopher A.,
Keku Temitope O.,
Kato Ikuko,
Palmer Julie R.,
van den Berg David,
Wilkens Lynne R.,
Burnett Terrilea,
Conti David V.,
Schumacher Fredrick R.,
Signorello Lisa B.,
Blot William J.,
Zanetti Krista A.,
Harris Curtis,
Pande Mala,
Berndt Sonja I.,
Newcomb Polly A.,
West Dee W.,
Haile Robert,
Stram Daniel O.,
Figueiredo Jane C.,
Le Marchand Loïc
Publication year - 2017
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30687
Subject(s) - genome wide association study , odds ratio , allele , colorectal cancer , genetic association , genetics , population , case control study , biology , oncology , medicine , single nucleotide polymorphism , cancer , genotype , gene , environmental health
Genome‐wide association studies (GWAS) in ethnic/racial minority populations can help to fine‐map previously identified risk regions or discover new risk loci because of the genetic diversity in these populations. We conducted a GWAS of colorectal cancer (CRC) in 6,597 African Americans (1,894 cases and 4,703 controls) (Stage 1) and followed up the most promising markers in a replication set of 2,041 participants of African descent (891 cases and 1,150 controls) (Stage 2). We identified a novel variant, rs56848936 in the gene SYMPK at 19q13.3, associated with colon cancer risk (odds ratio 0.61 for the risk allele G, p = 2.4 × 10 −8 ). The frequency of the G allele was 0.06 in African Americans, compared to <0.01 in Europeans, Asians and Amerindians in the 1000 Genomes project. In addition, a variant previously identified through fine‐mapping in this GWAS in the region 19q13.1, rs7252505, was confirmed to be more strongly associated with CRC in the African American replication set than the variant originally reported in Europeans (rs10411210). The association between rs7252505 and CRC was of borderline significance ( p = 0.05) in a Hispanic population GWAS with 1,611 CRC cases and 4,330 controls. With the three datasets combined, the odds ratio was 0.84 for the risk allele A (95% confidence interval 0.79–0.89, p = 3.7 × 10 −8 ). This study further highlights the importance of conducting GWAS studies in diverse ancestry populations.