title: A genome-wide association study for colorectal cancer identifies a risk locus in 14q23.1.
abstract: Over 50 loci associated with colorectal cancer (CRC) have been uncovered by genome-wide association studies (GWAS). Identifying additional loci has the potential to help elucidate aspects of the underlying biological processes leading to better understanding of the pathogenesis of the disease. We re-evaluated a GWAS by excluding controls that have family history of CRC or personal history of colorectal polyps, as we hypothesized that their inclusion reduces power to detect associations. This is supported empirically and through simulations. Two-phase GWAS analysis was performed in a total of 16,517 cases and 14,487 controls. We identified rs17094983, a SNP associated with risk of CRC [p = 2.5 × 10(-10); odds ratio estimated by re-including all controls (OR) = 0.87, 95% confidence interval (CI) 0.83-0.91; minor allele frequency (MAF) = 13%]. Results were replicated in samples of African descent (1894 cases and 4703 controls; p = 0.01; OR = 0.86, 95% CI 0.77-0.97; MAF = 16 %). Gene expression data in 195 colon adenocarcinomas and 59 normal colon tissues from two different studies revealed that this locus has genotypes that are associated with RTN1 (Reticulon 1) expression (p = 0.001), a protein-coding gene involved in survival and proliferation of cancer cells which is highly expressed in normal colon tissues but has significantly reduced expression in tumor cells (p = 1.3 × 10(-8)).
authors.affiliation: Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lemire
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Conghui
authors.initials: C
authors.lastname: Qu
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii.
authors.forename: Lenora W M
authors.initials: LWM
authors.lastname: Loo
authors.affiliation: Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.
authors.forename: Syed H E
authors.initials: SHE
authors.lastname: Zaidi
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii.
authors.forename: Hansong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Occupational and Environmental Epidemiology Branch, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
authors.affiliation: Service de Génétique Médicale, CHU Nantes, Nantes, France.|EA 4273, Faculté de médecine, Université de Nantes, Nantes, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bézieau
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.|Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner
authors.affiliation: American Cancer Society, Atlanta, GA, USA.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Campbell
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.|Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chan
authors.affiliation: Division of Cancer Epidemiology, Unit of Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Du
authors.affiliation: USC Norris Comprehensive Cancer Center, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Edlund
authors.affiliation: Samuel Lunenfeld Research Institute, Toronto, ON M5S 1X5, Canada.|Division of General Surgery, Toronto General Hospital, Toronto, ON M5G 2C4, Canada.
authors.forename: Steven
authors.initials: S
authors.lastname: Gallinger
authors.affiliation: Department of Medicine, Division of Oncology, Stanford University, California, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Haile
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Tabitha A
authors.initials: TA
authors.lastname: Harrison
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hoffmeister
authors.affiliation: Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.affiliation: Department of Preventive Medicine and the Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Illinois.
authors.forename: Lifang
authors.initials: L
authors.lastname: Hou
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.|Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Li
authors.initials: L
authors.lastname: Hsu
authors.affiliation: American Cancer Society, Atlanta, GA, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Jacobs
authors.affiliation: Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jenkins
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Jihyoun
authors.initials: J
authors.lastname: Jeon
authors.affiliation: Service de Génétique Médicale, CHU Nantes, Nantes, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Küry
authors.affiliation: Case Comprehensive Cancer Center and Swetland Center for Environmental Health, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Scottsdale, Arizona.
authors.forename: Noralane M
authors.initials: NM
authors.lastname: Lindor
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.|Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington.
authors.forename: Polly A
authors.initials: PA
authors.lastname: Newcomb
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.|Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington.|Centre for Public Health Research, Massey University, Wellington, New Zealand.
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
authors.affiliation: Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa, Israel.|Clalit Health Services National Cancer Control Center, Haifa, Israel.|Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Gad
authors.initials: G
authors.lastname: Rennert
authors.affiliation: Division of Cancer Epidemiology, Unit of Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Rudolph
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Schoen
authors.affiliation: USC Norris Comprehensive Cancer Center, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Fredrick R
authors.initials: FR
authors.lastname: Schumacher
authors.affiliation: Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Seminara
authors.affiliation: Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Australia.|Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.|Human Genetics Foundation (HuGeF), Torino, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Severi
authors.affiliation: Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, UT, USA.
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.|Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington.
authors.forename: Emily
authors.initials: E
authors.lastname: White
authors.affiliation: Discipline of Genetics, Memorial University of Newfoundland, St. John's, NF A1B 3V6, Canada.
authors.forename: Michael O
authors.initials: MO
authors.lastname: Woods
authors.affiliation: Cancer Care Ontario, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Michelle
authors.initials: M
authors.lastname: Cotterchio
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii.
authors.forename: Loic Le
authors.initials: LL
authors.lastname: Marchand
authors.affiliation: USC Norris Comprehensive Cancer Center, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Graham
authors.initials: G
authors.lastname: Casey
authors.affiliation: USC Norris Comprehensive Cancer Center, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.|USC Norris Comprehensive Cancer Center, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Steven B
authors.initials: SB
authors.lastname: Gruber
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.|School of Public Health, University of Washington, Seattle, Washington.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Peters
authors.affiliation: Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, ON M5S 1A1, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A1, Canada.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hudson
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics*; D000368:Aged; D016022:Case-Control Studies; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors