title: Genome-wide association study of colorectal cancer in Hispanics.
abstract: Genome-wide association studies (GWAS) have identified 58 susceptibility alleles across 37 regions associated with the risk of colorectal cancer (CRC) with P < 5×10(-8) Most studies have been conducted in non-Hispanic whites and East Asians; however, the generalizability of these findings and the potential for ethnic-specific risk variation in Hispanic and Latino (HL) individuals have been largely understudied. We describe the first GWAS of common genetic variation contributing to CRC risk in HL (1611 CRC cases and 4330 controls). We also examine known susceptibility alleles and implement imputation-based fine-mapping to identify potential ethnicity-specific association signals in known risk regions. We discovered 17 variants across 4 independent regions that merit further investigation due to suggestive CRC associations (P < 1×10(-6)) at 1p34.3 (rs7528276; Odds Ratio (OR) = 1.86 [95% confidence interval (CI): 1.47-2.36); P = 2.5×10(-7)], 2q23.3 (rs1367374; OR = 1.37 (95% CI: 1.21-1.55); P = 4.0×10(-7)), 14q24.2 (rs143046984; OR = 1.65 (95% CI: 1.36-2.01); P = 4.1×10(-7)) and 16q12.2 [rs142319636; OR = 1.69 (95% CI: 1.37-2.08); P=7.8×10(-7)]. Among the 57 previously published CRC susceptibility alleles with minor allele frequency ≥1%, 76.5% of SNPs had a consistent direction of effect and 19 (33.3%) were nominally statistically significant (P < 0.05). Further, rs185423955 and rs60892987 were identified as novel secondary susceptibility variants at 3q26.2 (P = 5.3×10(-5)) and 11q12.2 (P = 6.8×10(-5)), respectively. Our findings demonstrate the importance of fine mapping in HL. These results are informative for variant prioritization in functional studies and future risk prediction modeling in minority populations.
authors.affiliation: Department of Preventive Medicine.|University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.|Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL 33612, USA.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Schmit
authors.affiliation: Department of Preventive Medicine.|University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Fredrick R
authors.initials: FR
authors.lastname: Schumacher
authors.affiliation: Department of Preventive Medicine.|University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Edlund
authors.affiliation: Department of Preventive Medicine.|University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: David V
authors.initials: DV
authors.lastname: Conti
authors.affiliation: Department of Preventive Medicine.|University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Ugonna
authors.initials: U
authors.lastname: Ihenacho
authors.affiliation: Department of Preventive Medicine.|University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Peggy
authors.initials: P
authors.lastname: Wan
authors.affiliation: Department of Preventive Medicine.
authors.forename: David
authors.initials: D
authors.lastname: Van Den Berg
authors.affiliation: Department of Preventive Medicine.|University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Graham
authors.initials: G
authors.lastname: Casey
authors.affiliation: Department of Biology, Claremont McKenna College, Claremont, CA 91711, USA.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Fortini
authors.affiliation: Department of Preventive Medicine.|University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Heinz-Josef
authors.initials: HJ
authors.lastname: Lenz
authors.affiliation: Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Sección XVI, Tlalpan, 14000 México City, México.|Instituto de Investigaciones Biomédicas, UNAM. Unidad de Biología Molecular y Medicina Genómica, UNAM/INCMNSZ, Coyoacán, 04510 México City, México.
authors.forename: Teresa
authors.initials: T
authors.lastname: Tusié-Luna
authors.affiliation: Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Sección XVI, Tlalpan, 14000 México City, México.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Aguilar-Salinas
authors.affiliation: Universidad Autónoma Metropolitana, Tlalpan 14387, México City, México.
authors.forename: Hortensia
authors.initials: H
authors.lastname: Moreno-Macías
authors.affiliation: Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Sección XVI, Tlalpan, 14000 México City, México.|Instituto de Investigaciones Biomédicas, UNAM. Unidad de Biología Molecular y Medicina Genómica, UNAM/INCMNSZ, Coyoacán, 04510 México City, México.
authors.forename: Alicia
authors.initials: A
authors.lastname: Huerta-Chagoya
authors.affiliation: Universidad Autónoma Metropolitana, Tlalpan 14387, México City, México.
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Ordóñez-Sánchez
authors.affiliation: Universidad Autónoma Metropolitana, Tlalpan 14387, México City, México.
authors.forename: Rosario
authors.initials: R
authors.lastname: Rodríguez-Guillén
authors.affiliation: Universidad Autónoma Metropolitana, Tlalpan 14387, México City, México.
authors.forename: Ivette
authors.initials: I
authors.lastname: Cruz-Bautista
authors.affiliation: Universidad Autónoma Metropolitana, Tlalpan 14387, México City, México.
authors.forename: Maribel
authors.initials: M
authors.lastname: Rodríguez-Torres
authors.affiliation: Universidad Autónoma Metropolitana, Tlalpan 14387, México City, México.
authors.forename: Linda Liliana
authors.initials: LL
authors.lastname: Muñóz-Hernández
authors.affiliation: Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Sección XVI, Tlalpan, 14000 México City, México.
authors.forename: Olimpia
authors.initials: O
authors.lastname: Arellano-Campos
authors.affiliation: Universidad Autónoma Metropolitana, Tlalpan 14387, México City, México.
authors.forename: Donají
authors.initials: D
authors.lastname: Gómez
authors.affiliation: Universidad Autónoma Metropolitana, Tlalpan 14387, México City, México.
authors.forename: Ulices
authors.initials: U
authors.lastname: Alvirde
authors.affiliation: Unidad de Investigación en Diabetes, Instituto Nacional de Salud Pública, México City, México.|Centro de Estudios en Diabetes, 01120 México City, México and.
authors.forename: Clicerio
authors.initials: C
authors.lastname: González-Villalpando
authors.affiliation: Centro de Estudios en Diabetes, 01120 México City, México and.
authors.forename: María Elena
authors.initials: ME
authors.lastname: González-Villalpando
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USA.
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.affiliation: Department of Preventive Medicine.|University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.affiliation: Department of Preventive Medicine.|University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Jane C
authors.initials: JC
authors.lastname: Figueiredo
mesh_terms: D000368:Aged; D000483:Alleles; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged