title: Novel colon cancer susceptibility variants identified from a genome-wide association study in African Americans.
abstract: 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.
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI.
authors.forename: Hansong
authors.identifier: 0000-0001-7589-3163
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL.|Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL.|Department of Preventive Medicine and USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Schmit
authors.affiliation: Department of Preventive Medicine and USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.affiliation: Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC.
authors.forename: Temitope O
authors.initials: TO
authors.lastname: Keku
authors.affiliation: Wayne State University Karmanos Cancer Institute, Detroit, MI.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Kato
authors.affiliation: Slone Epidemiology Center at Boston University, Boston, MA.
authors.forename: Julie R
authors.initials: JR
authors.lastname: Palmer
authors.affiliation: Department of Preventive Medicine and USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
authors.forename: David
authors.initials: D
authors.lastname: van den Berg
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI.
authors.forename: Lynne R
authors.initials: LR
authors.lastname: Wilkens
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI.
authors.forename: Terrilea
authors.initials: T
authors.lastname: Burnett
authors.affiliation: Department of Preventive Medicine and USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
authors.forename: David V
authors.initials: DV
authors.lastname: Conti
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH.
authors.forename: Fredrick R
authors.initials: FR
authors.lastname: Schumacher
authors.affiliation: Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Lisa B
authors.initials: LB
authors.lastname: Signorello
authors.affiliation: Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN.
authors.forename: William J
authors.initials: WJ
authors.lastname: Blot
authors.affiliation: Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Krista A
authors.initials: KA
authors.lastname: Zanetti
authors.affiliation: Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Curtis
authors.initials: C
authors.lastname: Harris
authors.affiliation: Department of Gastroenterology, Hepatology & Nutrition, the University of Texas M. D. Anderson Cancer Center, Houston, TX.
authors.forename: Mala
authors.initials: M
authors.lastname: Pande
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
authors.affiliation: Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA.
authors.forename: Polly A
authors.initials: PA
authors.lastname: Newcomb
authors.affiliation: Cancer Prevention Institute of California, Fremont, CA.
authors.forename: Dee W
authors.initials: DW
authors.lastname: West
authors.affiliation: Stanford Cancer Institute, Stanford, CA.
authors.forename: Robert
authors.initials: R
authors.lastname: Haile
authors.affiliation: Department of Preventive Medicine and USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Stram
authors.affiliation: Department of Preventive Medicine and USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA.|Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA.
authors.forename: Jane C
authors.initials: JC
authors.lastname: Figueiredo
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI.
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Marchand
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D003110:Colonic Neoplasms / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D009687:Nuclear Proteins; C101043:SYMPK protein, human
keywords: African American; Hispanic; colorectal cancer; common variant; minority