Genome-wide association study of colorectal cancer identifies six new susceptibility loci

Fredrick R Schumacher; Stephanie L Schmit; Shuo Jiao; Christopher K Edlund; Hansong Wang; Ben Zhang; Li Hsu; Shu-Chen Huang; Christopher P Fischer; John F Harju; Gregory E Idos; Flavio Lejbkowicz; Frank J Manion; Kevin McDonnell; Caroline E McNeil; Marilena Melas; Hedy S Rennert; Wei Shi; Duncan C Thomas; David J Van Den Berg; Carolyn M Hutter; Aaron K Aragaki; Katja Butterbach; Bette J Caan; Christopher S Carlson; Stephen J Chanock; Keith R Curtis; Charles S Fuchs; Manish Gala; Edward L Giovannucci; Stephanie M Gogarten; Richard B Hayes; Brian Henderson; David J Hunter; Rebecca D Jackson; Laurence N Kolonel; Charles Kooperberg; Sébastien Küry; Andrea LaCroix; Cathy C Laurie; Cecelia A Laurie; Mathieu Lemire; David Levine; Jing Ma; Karen W Makar; Conghui Qu; Darin Taverna; Cornelia M Ulrich; Kana Wu; Suminori Kono; Dee W West; Sonja I Berndt; Stéphane Bezieau; Hermann Brenner; Peter T Campbell; Andrew T Chan; Jenny Chang-Claude; Gerhard A Coetzee; David V Conti; David Duggan; Jane C Figueiredo; Barbara K Fortini; Steven J Gallinger; W James Gauderman; Graham Giles; Roger Green; Robert Haile; Tabitha A Harrison; Michael Hoffmeister; John L Hopper; Thomas J Hudson; Eric Jacobs; Motoki Iwasaki; Sun Ha Jee; Mark Jenkins; Wei-Hua Jia; Amit Joshi; Li Li; Noralene M Lindor; Keitaro Matsuo; Victor Moreno; Bhramar Mukherjee; Polly A Newcomb; John D Potter; Leon Raskin; Gad Rennert; Stephanie Rosse; Gianluca Severi; Robert E Schoen; Daniela Seminara; Xiao-Ou Shu; Martha L Slattery; Shoichiro Tsugane; Emily White; Yong-Bing Xiang; Brent W Zanke; Wei Zheng; Loic Le Marchand; Graham Casey; Stephen B Gruber; Ulrike Peters

doi:10.1038/ncomms8138

Genome-wide association study of colorectal cancer identifies six new susceptibility loci

Nat Commun. 2015 Jul 7:6:7138. doi: 10.1038/ncomms8138.

Authors

Fredrick R Schumacher¹, Stephanie L Schmit^{1

2}, Shuo Jiao³, Christopher K Edlund¹, Hansong Wang⁴, Ben Zhang⁵, Li Hsu³, Shu-Chen Huang¹, Christopher P Fischer⁶, John F Harju⁶, Gregory E Idos¹, Flavio Lejbkowicz^{7

8}, Frank J Manion⁶, Kevin McDonnell¹, Caroline E McNeil¹, Marilena Melas¹, Hedy S Rennert^{7

8}, Wei Shi⁹, Duncan C Thomas¹, David J Van Den Berg¹, Carolyn M Hutter¹⁰, Aaron K Aragaki³, Katja Butterbach¹¹, Bette J Caan¹², Christopher S Carlson³, Stephen J Chanock¹³, Keith R Curtis³, Charles S Fuchs^{14

15}, Manish Gala¹⁶, Edward L Giovannucci^{17

18}, Stephanie M Gogarten¹⁹, Richard B Hayes²⁰, Brian Henderson¹, David J Hunter²¹, Rebecca D Jackson²², Laurence N Kolonel²³, Charles Kooperberg³, Sébastien Küry²⁴, Andrea LaCroix³, Cathy C Laurie¹⁹, Cecelia A Laurie¹⁹, Mathieu Lemire²⁵, David Levine¹⁹, Jing Ma²⁶, Karen W Makar³, Conghui Qu³, Darin Taverna²⁷, Cornelia M Ulrich^{3

28

29}, Kana Wu³⁰, Suminori Kono³¹, Dee W West³², Sonja I Berndt¹³, Stéphane Bezieau³³, Hermann Brenner¹¹, Peter T Campbell³⁴, Andrew T Chan^{16

17}, Jenny Chang-Claude³⁵, Gerhard A Coetzee¹, David V Conti^{1

36}, David Duggan³⁷, Jane C Figueiredo¹, Barbara K Fortini¹, Steven J Gallinger³⁸, W James Gauderman¹, Graham Giles³⁹, Roger Green⁴⁰, Robert Haile⁴¹, Tabitha A Harrison³, Michael Hoffmeister¹¹, John L Hopper⁴², Thomas J Hudson⁴³, Eric Jacobs³⁴, Motoki Iwasaki⁴⁴, Sun Ha Jee⁴⁵, Mark Jenkins⁴⁶, Wei-Hua Jia⁴⁷, Amit Joshi⁴⁸, Li Li⁴⁹, Noralene M Lindor⁵⁰, Keitaro Matsuo³¹, Victor Moreno⁵¹, Bhramar Mukherjee⁵², Polly A Newcomb⁵³, John D Potter⁵³, Leon Raskin^{1

54

55}, Gad Rennert^{1

7

8

56}, Stephanie Rosse³, Gianluca Severi^{39

57}, Robert E Schoen⁵⁸, Daniela Seminara⁵⁹, Xiao-Ou Shu^{55

60}, Martha L Slattery⁶¹, Shoichiro Tsugane⁴⁴, Emily White³, Yong-Bing Xiang⁶², Brent W Zanke^{63

64}, Wei Zheng^{54

55}, Loic Le Marchand⁴, Graham Casey¹, Stephen B Gruber^{1

2}, Ulrike Peters³

Affiliations

¹ Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
² Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
³ Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98124, USA.
⁴ Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii 96822, USA.
⁵ Department of General Surgery, Third Military Medical University Southwest Hospital, Chongqing 400038, China.
⁶ University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48105, USA.
⁷ Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa 34361, Israel.
⁸ Clalit Health Services National Cancer Control Center, Haifa 34361, Israel.
⁹ Department of Surgery, Children's Hospital Los Angeles, Los Angeles, California 90027, USA.
¹⁰ Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20892, USA.
¹¹ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg 69121, Germany.
¹² Division of Research, Kaiser Permanente Medical Care Program of Northern California, Oakland, California 94612, USA.
¹³ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892-9776, USA.
¹⁴ Department of Medicine, Brigham and Women's Hospital, Brookline, Massachusetts 02115, USA.
¹⁵ Department of Medical Oncology, Dana-Farber Cancer Institute, Brookline, Massachusetts 02115, USA.
¹⁶ Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
¹⁷ Harvard Medical School, Boston, Massachusetts 02114, USA.
¹⁸ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
¹⁹ Department of Biostatistics, University of Washington, Seattle, Washington 98195, USA.
²⁰ Division of Epidemiology, Department of Population Health, New York University School of Medicine, New York, New York 10016, USA.
²¹ Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
²² Department of Medicine, Ohio State University, Columbus, Ohio 43210, USA.
²³ Office of Public Health Studies, University of Hawaii Manoa, Honolulu, Hawaii 96822, USA.
²⁴ Service de Génétique Médicale, CHU Nantes, Nantes 44093, France.
²⁵ Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada.
²⁶ Harvard School of Public Health, Boston, Massachusetts 02114, USA.
²⁷ Phoenix College, Phoenix, Arizona 85013, USA.
²⁸ Division of Preventive Oncology, German Cancer Research Center, Heidelberg 69120, Germany.
²⁹ Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington 98195, USA.
³⁰ Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
³¹ Department of Preventive Medicine, Kyushu University, Fukuoka 812-8582, Japan.
³² Cancer Registry of Greater California, Public Health Institute, Sacramento, California 95825, USA.
³³ Centre Hospitalier Universitaire Hotel-Dieu, Nantes, 44093, France.
³⁴ Epidemiology Research Program, American Cancer Society, Atlanta, Georgia 30329-4251, USA.
³⁵ Unit of Genetic Epidemiology, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg 69121, Germany.
³⁶ Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California 90089, USA.
³⁷ Genetic Basis of Human Disease Division, Translational Genomics Research Institute, Phoenix, Arizona 85004, USA.
³⁸ Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario M5T 3L9, Canada.
³⁹ Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria 3004, Australia.
⁴⁰ Discipline of Genetics, Memorial University of Newfoundland, St. John's, Newfoundland A1B 3V6, Canada.
⁴¹ Department of Medicine, Division of Oncology, Stanford University, Stanford, California 94305, USA.
⁴² Centre for MEGA Epidemiology, The University of Melbourne, Carlton, Victoria 3010, Australia.
⁴³ Department of Genomics, Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada.
⁴⁴ Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo 104-0045, Japan.
⁴⁵ Department of Epidemiology and Health Promotion, Graduate School of Public Health, Yonsei University, Seoul 120-749, South Korea.
⁴⁶ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria 3010, Australia.
⁴⁷ State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
⁴⁸ Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
⁴⁹ Department of Family Medicine and Community Health, Case Western Reserve University, Cleveland, Ohio 44106, USA.
⁵⁰ Department of Health Science Research, Mayo Clinic, Scottsdale, Arizona 85259, USA.
⁵¹ Cancer Epidemiology Service, Catalan Institute of Oncology, IDIBELL, 08908, Barcelona, Spain.
⁵² Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA.
⁵³ Cancer Prevention Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
⁵⁴ Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37203-1738, USA.
⁵⁵ Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37203-1738, USA.
⁵⁶ Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3200003, Israel.
⁵⁷ Human Genetics Foundation (HuGeF), Torino 10126, Italy.
⁵⁸ Department of Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA.
⁵⁹ Epidemiology and Genomics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
⁶⁰ Division of Epidemiology, Vanderbilt University School of Medicine, Nashville, Tennessee 37203-1738, USA.
⁶¹ Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA.
⁶² Department of Epidemiology, Shanghai Cancer Institute, Shanghai 2200-25, China.
⁶³ The University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
⁶⁴ Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario K1Y 4E9, Canada.

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.

Publication types

Meta-Analysis
Research Support, N.I.H., Extramural

MeSH terms

Case-Control Studies
Colorectal Neoplasms / genetics*
Genetic Predisposition to Disease*
Genome-Wide Association Study*
Humans
Odds Ratio
Polymorphism, Single Nucleotide

Abstract

Publication types

MeSH terms

Grants and funding