title: Genome-wide association study of colorectal cancer identifies six new susceptibility loci.
abstract: Genetic susceptibility to colorectal cancer is caused by rare pathogenic mutations and common genetic variants that contribute to familial risk. Here we report the results of a two-stage association study with 18,299 cases of colorectal cancer and 19,656 controls, with follow-up of the most statistically significant genetic loci in 4,725 cases and 9,969 controls from two Asian consortia. We describe six new susceptibility loci reaching a genome-wide threshold of P<5.0E-08. These findings provide additional insight into the underlying biological mechanisms of colorectal cancer and demonstrate the scientific value of large consortia-based genetic epidemiology studies.
authors.affiliation: Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Fredrick R
authors.initials: FR
authors.lastname: Schumacher
authors.affiliation: Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.|Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Schmit
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98124, USA.
authors.forename: Shuo
authors.initials: S
authors.lastname: Jiao
authors.affiliation: Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Edlund
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii 96822, USA.
authors.forename: Hansong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Third Military Medical University Southwest Hospital, Chongqing 400038, China.
authors.forename: Ben
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98124, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Hsu
authors.affiliation: Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Huang
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48105, USA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Fischer
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48105, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Harju
authors.affiliation: Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Idos
authors.affiliation: Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa 34361, Israel.|Clalit Health Services National Cancer Control Center, Haifa 34361, Israel.
authors.forename: Flavio
authors.initials: F
authors.lastname: Lejbkowicz
authors.affiliation: University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48105, USA.
authors.forename: Frank J
authors.identifier: http://orcid.org/0000-0003-1030-6348
authors.initials: FJ
authors.lastname: Manion
authors.affiliation: Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: McDonnell
authors.affiliation: Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: McNeil
authors.affiliation: Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Marilena
authors.initials: M
authors.lastname: Melas
authors.affiliation: Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa 34361, Israel.|Clalit Health Services National Cancer Control Center, Haifa 34361, Israel.
authors.forename: Hedy S
authors.initials: HS
authors.lastname: Rennert
authors.affiliation: Department of Surgery, Children's Hospital Los Angeles, Los Angeles, California 90027, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Duncan C
authors.initials: DC
authors.lastname: Thomas
authors.affiliation: Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Van Den Berg
authors.affiliation: Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20892, USA.
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Hutter
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98124, USA.
authors.forename: Aaron K
authors.initials: AK
authors.lastname: Aragaki
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg 69121, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Butterbach
authors.affiliation: Division of Research, Kaiser Permanente Medical Care Program of Northern California, Oakland, California 94612, USA.
authors.forename: Bette J
authors.initials: BJ
authors.lastname: Caan
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98124, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Carlson
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892-9776, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98124, USA.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Curtis
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Brookline, Massachusetts 02115, USA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Brookline, Massachusetts 02115, USA.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Fuchs
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
authors.forename: Manish
authors.initials: M
authors.lastname: Gala
authors.affiliation: Harvard Medical School, Boston, Massachusetts 02114, USA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: Edward L
authors.initials: EL
authors.lastname: Giovannucci
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Gogarten
authors.affiliation: Division of Epidemiology, Department of Population Health, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Hayes
authors.affiliation: Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Henderson
authors.affiliation: Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.affiliation: Department of Medicine, Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Jackson
authors.affiliation: Office of Public Health Studies, University of Hawaii Manoa, Honolulu, Hawaii 96822, USA.
authors.forename: Laurence N
authors.initials: LN
authors.lastname: Kolonel
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98124, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Kooperberg
authors.affiliation: Service de Génétique Médicale, CHU Nantes, Nantes 44093, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Küry
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98124, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: LaCroix
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Cathy C
authors.initials: CC
authors.lastname: Laurie
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Cecelia A
authors.initials: CA
authors.lastname: Laurie
authors.affiliation: Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lemire
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington 98195, USA.
authors.forename: David
authors.initials: D
authors.lastname: Levine
authors.affiliation: Harvard School of Public Health, Boston, Massachusetts 02114, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98124, USA.
authors.forename: Karen W
authors.initials: KW
authors.lastname: Makar
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98124, USA.
authors.forename: Conghui
authors.initials: C
authors.lastname: Qu
authors.affiliation: Phoenix College, Phoenix, Arizona 85013, USA.
authors.forename: Darin
authors.initials: D
authors.lastname: Taverna
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98124, USA.|Division of Preventive Oncology, German Cancer Research Center, Heidelberg 69120, Germany.|Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington 98195, USA.
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Ulrich
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Kana
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Preventive Medicine, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Suminori
authors.initials: S
authors.lastname: Kono
authors.affiliation: Cancer Registry of Greater California, Public Health Institute, Sacramento, California 95825, USA.
authors.forename: Dee W
authors.initials: DW
authors.lastname: West
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892-9776, USA.
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Berndt
authors.affiliation: Centre Hospitalier Universitaire Hotel-Dieu, Nantes, 44093, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bezieau
authors.affiliation: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg 69121, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner
authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta, Georgia 30329-4251, USA.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Campbell
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.|Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chan
authors.affiliation: Unit of Genetic Epidemiology, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg 69121, Germany.
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
authors.affiliation: Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Gerhard A
authors.initials: GA
authors.lastname: Coetzee
authors.affiliation: Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.|Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: David V
authors.initials: DV
authors.lastname: Conti
authors.affiliation: Genetic Basis of Human Disease Division, Translational Genomics Research Institute, Phoenix, Arizona 85004, USA.
authors.forename: David
authors.initials: D
authors.lastname: Duggan
authors.affiliation: Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Jane C
authors.initials: JC
authors.lastname: Figueiredo
authors.affiliation: Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Fortini
authors.affiliation: Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario M5T 3L9, Canada.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Gallinger
authors.affiliation: Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: W James
authors.initials: WJ
authors.lastname: Gauderman
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria 3004, Australia.
authors.forename: Graham
authors.initials: G
authors.lastname: Giles
authors.affiliation: Discipline of Genetics, Memorial University of Newfoundland, St. John's, Newfoundland A1B 3V6, Canada.
authors.forename: Roger
authors.initials: R
authors.lastname: Green
authors.affiliation: Department of Medicine, Division of Oncology, Stanford University, Stanford, California 94305, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Haile
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98124, USA.
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 69121, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hoffmeister
authors.affiliation: Centre for MEGA Epidemiology, The University of Melbourne, Carlton, Victoria 3010, Australia.
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.affiliation: Department of Genomics, Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada.
authors.forename: Thomas J
authors.identifier: http://orcid.org/0000-0002-1376-4849
authors.initials: TJ
authors.lastname: Hudson
authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta, Georgia 30329-4251, USA.
authors.forename: Eric
authors.identifier: http://orcid.org/0000-0002-8458-7659
authors.initials: E
authors.lastname: Jacobs
authors.affiliation: Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo 104-0045, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Iwasaki
authors.affiliation: Department of Epidemiology and Health Promotion, Graduate School of Public Health, Yonsei University, Seoul 120-749, South Korea.
authors.forename: Sun Ha
authors.initials: SH
authors.lastname: Jee
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Jenkins
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Jia
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Joshi
authors.affiliation: Department of Family Medicine and Community Health, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Health Science Research, Mayo Clinic, Scottsdale, Arizona 85259, USA.
authors.forename: Noralene M
authors.initials: NM
authors.lastname: Lindor
authors.affiliation: Department of Preventive Medicine, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Cancer Epidemiology Service, Catalan Institute of Oncology, IDIBELL, 08908, Barcelona, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Moreno
authors.affiliation: Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Bhramar
authors.initials: B
authors.lastname: Mukherjee
authors.affiliation: Cancer Prevention Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
authors.forename: Polly A
authors.initials: PA
authors.lastname: Newcomb
authors.affiliation: Cancer Prevention Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
authors.affiliation: Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.|Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37203-1738, USA.|Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37203-1738, USA.
authors.forename: Leon
authors.initials: L
authors.lastname: Raskin
authors.affiliation: Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.|Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa 34361, Israel.|Clalit Health Services National Cancer Control Center, Haifa 34361, Israel.|Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3200003, Israel.
authors.forename: Gad
authors.initials: G
authors.lastname: Rennert
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98124, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Rosse
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria 3004, Australia.|Human Genetics Foundation (HuGeF), Torino 10126, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Severi
authors.affiliation: Department of Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Schoen
authors.affiliation: Epidemiology and Genomics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Seminara
authors.affiliation: Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37203-1738, USA.|Division of Epidemiology, Vanderbilt University School of Medicine, Nashville, Tennessee 37203-1738, USA.
authors.forename: Xiao-Ou
authors.initials: XO
authors.lastname: Shu
authors.affiliation: Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA.
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
authors.affiliation: Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo 104-0045, Japan.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Tsugane
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98124, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: White
authors.affiliation: Department of Epidemiology, Shanghai Cancer Institute, Shanghai 2200-25, China.
authors.forename: Yong-Bing
authors.initials: YB
authors.lastname: Xiang
authors.affiliation: The University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.|Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario K1Y 4E9, Canada.
authors.forename: Brent W
authors.initials: BW
authors.lastname: Zanke
authors.affiliation: Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37203-1738, USA.|Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37203-1738, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii 96822, USA.
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.affiliation: Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Graham
authors.initials: G
authors.lastname: Casey
authors.affiliation: Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.|Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gruber
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98124, USA.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Peters
mesh_terms: D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide