Meta-Analysis

. 2023 Jan;55(1):89-99.

doi: 10.1038/s41588-022-01222-9. Epub 2022 Dec 20.

Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries

Ceres Fernandez-Rozadilla^#^{1

2}, Maria Timofeeva^#^{3

4}, Zhishan Chen^#⁵, Philip Law^#⁶, Minta Thomas^#⁷, Stephanie Schmit^#^{8

9}, Virginia Díez-Obrero^#^{10

11

12

13}, Li Hsu^#^{7

14}, Juan Fernandez-Tajes¹, Claire Palles¹⁵, Kitty Sherwood¹, Sarah Briggs¹⁶, Victoria Svinti³, Kevin Donnelly³, Susan Farrington³, James Blackmur³, Peter Vaughan-Shaw³, Xiao-Ou Shu⁵, Jirong Long⁵, Qiuyin Cai⁵, Xingyi Guo^{5

17}, Yingchang Lu⁵, Peter Broderick⁶, James Studd⁶, Jeroen Huyghe⁷, Tabitha Harrison⁷, David Conti¹⁸, Christopher Dampier¹⁹, Mathew Devall¹⁹, Fredrick Schumacher^{20

21}, Marilena Melas²², Gad Rennert^{23

24

25}, Mireia Obón-Santacana^{10

11

26}, Vicente Martín-Sánchez^{12

27}, Ferran Moratalla-Navarro^{10

11

12

13}, Jae Hwan Oh²⁸, Jeongseon Kim²⁹, Sun Ha Jee³⁰, Keum Ji Jung³⁰, Sun-Seog Kweon³¹, Min-Ho Shin³¹, Aesun Shin^{32

33}, Yoon-Ok Ahn³², Dong-Hyun Kim³⁴, Isao Oze³⁵, Wanqing Wen⁵, Keitaro Matsuo^{36

37}, Koichi Matsuda³⁸, Chizu Tanikawa³⁹, Zefang Ren⁴⁰, Yu-Tang Gao⁴¹, Wei-Hua Jia⁴², John Hopper^{43

44}, Mark Jenkins⁴³, Aung Ko Win⁴³, Rish Pai⁴⁵, Jane Figueiredo^{18

46}, Robert Haile⁴⁷, Steven Gallinger⁴⁸, Michael Woods⁴⁹, Polly Newcomb^{7

50}, David Duggan⁵¹, Jeremy Cheadle⁵², Richard Kaplan⁵³, Timothy Maughan⁵⁴, Rachel Kerr⁵⁵, David Kerr⁵⁶, Iva Kirac⁵⁷, Jan Böhm⁵⁸, Lukka-Pekka Mecklin⁵⁹, Pekka Jousilahti⁶⁰, Paul Knekt⁶⁰, Lauri Aaltonen^{61

62}, Harri Rissanen⁶³, Eero Pukkala^{64

65}, Johan Eriksson^{66

67

68}, Tatiana Cajuso^{61

62}, Ulrika Hänninen^{61

62}, Johanna Kondelin^{61

62}, Kimmo Palin^{61

62}, Tomas Tanskanen^{61

62}, Laura Renkonen-Sinisalo⁶⁹, Brent Zanke⁷⁰, Satu Männistö⁶³, Demetrius Albanes⁷¹, Stephanie Weinstein⁷¹, Edward Ruiz-Narvaez⁷², Julie Palmer^{73

74}, Daniel Buchanan^{75

76

77}, Elizabeth Platz⁷⁸, Kala Visvanathan⁷⁸, Cornelia Ulrich⁷⁹, Erin Siegel⁸⁰, Stefanie Brezina⁸¹, Andrea Gsur⁸¹, Peter Campbell⁸², Jenny Chang-Claude^{83

84}, Michael Hoffmeister⁸⁵, Hermann Brenner^{85

86

87}, Martha Slattery⁸⁸, John Potter^{7

89}, Konstantinos Tsilidis^{90

91}, Matthias Schulze^{92

93}, Marc Gunter⁹⁴, Neil Murphy⁹⁴, Antoni Castells⁹⁵, Sergi Castellví-Bel⁹⁵, Leticia Moreira⁹⁵, Volker Arndt⁸⁵, Anna Shcherbina⁹⁶, Mariana Stern^{97

98}, Bens Pardamean⁹⁹, Timothy Bishop¹⁰⁰, Graham Giles^{43

101

102}, Melissa Southey^{101

102

103}, Gregory Idos¹⁰⁴, Kevin McDonnell^{24

25

104}, Zomoroda Abu-Ful²³, Joel Greenson^{24

25

105}, Katerina Shulman²³, Flavio Lejbkowicz^{23

25

106}, Kenneth Offit^{107

108}, Yu-Ru Su¹⁰⁹, Robert Steinfelder⁷, Temitope Keku¹¹⁰, Bethany van Guelpen^{111

112}, Thomas Hudson¹¹³, Heather Hampel¹¹⁴, Rachel Pearlman¹¹⁴, Sonja Berndt⁷¹, Richard Hayes¹¹⁵, Marie Elena Martinez^{116

117}, Sushma Thomas¹¹⁸, Douglas Corley^{119

120}, Paul Pharoah¹²¹, Susanna Larsson¹²², Yun Yen¹²³, Heinz-Josef Lenz¹²⁴, Emily White^{7

125}, Li Li²¹, Kimberly Doheny¹²⁶, Elizabeth Pugh¹²⁶, Tameka Shelford¹²⁶, Andrew Chan^{127

128

129

130

131

132}, Marcia Cruz-Correa¹³³, Annika Lindblom^{134

135}, David Hunter^{131

136}, Amit Joshi^{127

131}, Clemens Schafmayer¹³⁷, Peter Scacheri¹³⁸, Anshul Kundaje^{96

139}, Deborah Nickerson¹⁴⁰, Robert Schoen¹⁴¹, Jochen Hampe¹⁴², Zsofia Stadler^{108

143}, Pavel Vodicka^{144

145

146}, Ludmila Vodickova^{144

145

146}, Veronika Vymetalkova^{144

145

146}, Nickolas Papadopoulos^{147

148

149}, Chistopher Edlund¹⁸, William Gauderman¹⁸, Duncan Thomas¹⁸, David Shibata¹⁵⁰, Amanda Toland¹⁵¹, Sanford Markowitz¹⁵², Andre Kim¹⁸, Stephen Chanock⁷¹, Franzel van Duijnhoven¹⁵³, Edith Feskens¹⁵⁴, Lori Sakoda^{7

119}, Manuela Gago-Dominguez^{155

156}, Alicja Wolk¹²², Alessio Naccarati^{157

158}, Barbara Pardini^{157

158}, Liesel FitzGerald^{101

159}, Soo Chin Lee¹⁶⁰, Shuji Ogino^{131

161

162

163}, Stephanie Bien⁷, Charles Kooperberg⁷, Christopher Li⁷, Yi Lin⁷, Ross Prentice^{7

164}, Conghui Qu⁷, Stéphane Bézieau¹⁶⁵, Catherine Tangen¹⁶⁶, Elaine Mardis¹⁶⁷, Taiki Yamaji¹⁶⁸, Norie Sawada¹⁶⁹, Motoki Iwasaki^{168

169}, Christopher Haiman¹⁷⁰, Loic Le Marchand¹⁷¹, Anna Wu¹⁷², Chenxu Qu¹⁷³, Caroline McNeil¹⁷³, Gerhard Coetzee¹⁷⁴, Caroline Hayward¹⁷⁵, Ian Deary¹⁷⁶, Sarah Harris¹⁷⁶, Evropi Theodoratou¹⁷⁷, Stuart Reid³, Marion Walker³, Li Yin Ooi^{3

178}, Victor Moreno^{10

11

12

13}, Graham Casey¹⁹, Stephen Gruber¹⁰⁴, Ian Tomlinson^{179

180}, Wei Zheng¹⁸¹, Malcolm Dunlop¹⁸², Richard Houlston¹⁸³, Ulrike Peters^{184

185}

Affiliations

¹ Edinburgh Cancer Research Centre, Institute of Genomics and Cancer, University of Edinburgh, Edinburgh, UK.
² Genomic Medicine Group, Instituto de Investigacion Sanitaria de Santiago, Santiago de Compostela, Spain.
³ Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
⁴ Danish Institute for Advanced Study, Department of Public Health, University of Southern Denmark, Odense, Denmark.
⁵ Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA.
⁶ Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
⁷ Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
⁸ Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.
⁹ Population and Cancer Prevention Program, Case Comprehensive Cancer Center, Cleveland, OH, USA.
¹⁰ Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute, Barcelona, Spain.
¹¹ Oncology Data Analytics Program, Catalan Institute of Oncology, Barcelona, Spain.
¹² Consortium for Biomedical Research in Epidemiology and Public Health, Madrid, Madrid, Spain.
¹³ Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
¹⁴ Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.
¹⁵ Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
¹⁶ Department of Public Health, Richard Doll Building, University of Oxford, Oxford, UK.
¹⁷ Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN, USA.
¹⁸ Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
¹⁹ Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
²⁰ Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
²¹ Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
²² The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
²³ Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel.
²⁴ Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
²⁵ Clalit National Cancer Control Center, Haifa, Israel.
²⁶ Consortium for Biomedical Research in Epidemiology and Public Health, Madrid, Spain.
²⁷ Biomedicine Institute, University of León, León, Spain.
²⁸ Center for Colorectal Cancer, National Cancer Center Hospital, National Cancer Center, Gyeonggi-do, South Korea.
²⁹ Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Gyeonggi-do, South Korea.
³⁰ Department of Epidemiology and Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, South Korea.
³¹ Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, South Korea.
³² Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea.
³³ Cancer Research Institute, Seoul National University, Seoul, South Korea.
³⁴ Department of Social and Preventive Medicine, Hallym University College of Medicine, Okcheon-dong, South Korea.
³⁵ Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
³⁶ Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, Nagoya, Japan.
³⁷ Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
³⁸ Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan.
³⁹ Laboratory of Genome Technology, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
⁴⁰ School of Public Health, Sun Yat-sen University, Guangzhou, China.
⁴¹ State Key Laboratory of Oncogenes and Related Genes and Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
⁴² State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
⁴³ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
⁴⁴ Department of Epidemiology, School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, South Korea.
⁴⁵ Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
⁴⁶ Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁴⁷ Division of Oncology, Department of Medicine, Cedars-Sinai Cancer Research Center for Health Equity, Los Angeles, CA, USA.
⁴⁸ Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
⁴⁹ Division of Biomedical Sciences, Memorial University of Newfoundland, St. John, Ontario, Canada.
⁵⁰ School of Public Health, University of Washington, Seattle, WA, USA.
⁵¹ City of Hope National Medical Center, Translational Genomics Research Institute, Phoenix, AZ, USA.
⁵² Institute of Medical Genetics, Cardiff University, Cardiff, UK.
⁵³ MRC Clinical Trials Unit, Medical Research Council, Cardiff, UK.
⁵⁴ MRC Institute for Radiation Oncology, University of Oxford, Oxford, UK.
⁵⁵ Department of Oncology, University of Oxford, Oxford, UK.
⁵⁶ Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
⁵⁷ Department of Surgical Oncology, University Hospital for Tumors, Sestre milosrdnice University Hospital Center, Zagreb, Croatia.
⁵⁸ Department of Pathology, Central Finland Health Care District, Jyväskylä, Finland.
⁵⁹ Central Finland Health Care District, Jyväskylä, Finland.
⁶⁰ Department of Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland.
⁶¹ Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland.
⁶² Genome-Scale Biology Research Program, University of Helsinki, Helsinki, Finland.
⁶³ Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland.
⁶⁴ Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland.
⁶⁵ Faculty of Social Sciences, Tampere University, Tampere, Finland.
⁶⁶ Folkhälsan Research Centre, University of Helsinki, Helsinki, Finland.
⁶⁷ Human Potential Translational Research Programme, National University of Singapore, Singapore, Singapore.
⁶⁸ Unit of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁶⁹ Department of Surgery, Abdominal Centre, Helsinki University Hospital, Helsinki, Finland.
⁷⁰ Department of Oncology, University of Toronto, Toronto, Ontario, Canada.
⁷¹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
⁷² Department of Nutritional Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
⁷³ Slone Epidemiology Center at Boston University, Boston, MA, USA.
⁷⁴ Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
⁷⁵ Colorectal Oncogenomics Group, Department of Clinical Pathology, University of Melbourne, Parkville, Victoria, Australia.
⁷⁶ University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, Victoria, Australia.
⁷⁷ Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Victoria, Australia.
⁷⁸ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁷⁹ Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA.
⁸⁰ Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
⁸¹ Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Vienna, Austria.
⁸² Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY, USA.
⁸³ Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
⁸⁴ University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg, Hamburg, Germany.
⁸⁵ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
⁸⁶ Division of Preventive Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany.
⁸⁷ German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany.
⁸⁸ Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.
⁸⁹ Research Centre for Hauora and Health, Massey University, Wellington, New Zealand.
⁹⁰ Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
⁹¹ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
⁹² Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
⁹³ Institute of Nutritional Science, University of Potsdam, Potsdam, Germany.
⁹⁴ Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.
⁹⁵ Gastroenterology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, University of Barcelona, Barcelona, Spain.
⁹⁶ Department of Genetics, Stanford University, Stanford, CA, USA.
⁹⁷ Department of Population and Public Health Sciences, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁹⁸ Jeonnam Regional Cancer Center, Chonnam National University Hwasun Hospital, Hwasun, South Korea.
⁹⁹ Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
¹⁰⁰ Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.
¹⁰¹ Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
¹⁰² Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
¹⁰³ Department of Clinical Pathology, University of Melbourne, Melbourne, Victoria, Australia.
¹⁰⁴ Department of Medical Oncology and Center For Precision Medicine, City of Hope National Medical Center, Duarte, CA, USA.
¹⁰⁵ Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
¹⁰⁶ Clalit Health Services, Personalized Genomic Service, Lady Davis Carmel Medical Center, Haifa, Israel.
¹⁰⁷ Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
¹⁰⁸ Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
¹⁰⁹ Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
¹¹⁰ Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA.
¹¹¹ Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden.
¹¹² Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden.
¹¹³ Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
¹¹⁴ Division of Human Genetics, Department of Internal Medicine, Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
¹¹⁵ Division of Epidemiology, Department of Population Health, New York University School of Medicine, New York, NY, USA.
¹¹⁶ Population Sciences, Disparities and Community Engagement, University of California San Diego Moores Cancer Center, La Jolla, CA, USA.
¹¹⁷ Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA.
¹¹⁸ Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
¹¹⁹ Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
¹²⁰ Department of Gastroenterology, Kaiser Permanente Medical Center, San Francisco, CA, USA.
¹²¹ Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
¹²² Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
¹²³ Taipei Medical University, Taipei, Taiwan.
¹²⁴ Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
¹²⁵ Department of Epidemiology, University of Washington School of Public Health, Seattle, WA, USA.
¹²⁶ Center for Inherited Disease Research, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹²⁷ Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
¹²⁸ Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
¹²⁹ Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹³⁰ Broad Institute of Harvard and MIT, Cambridge, MA, USA.
¹³¹ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
¹³² Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
¹³³ Comprehensive Cancer Center, University of Puerto Rico, San Juan, Puerto Rico.
¹³⁴ Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
¹³⁵ Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
¹³⁶ Nuffield Department of Population Health, University of Oxford, Oxford, UK.
¹³⁷ Department of General Surgery, University Hospital Rostock, Rostock, Germany.
¹³⁸ Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA.
¹³⁹ Department of Computer Science, Stanford University, Stanford, CA, USA.
¹⁴⁰ Department of Genome Sciences, University of Washington, Seattle, WA, USA.
¹⁴¹ Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
¹⁴² Department of Medicine I, University Hospital Dresden, Technische Universität Dresden, Dresden, Germany.
¹⁴³ Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
¹⁴⁴ Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic.
¹⁴⁵ Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic.
¹⁴⁶ Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic.
¹⁴⁷ Department of Oncology Ludwig Center at the Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁴⁸ Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁴⁹ Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
¹⁵⁰ Department of Surgery, University of Tennessee Health Science Center, Memphis, TN, USA.
¹⁵¹ Departments of Cancer Biology and Genetics and Internal Medicine, Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA.
¹⁵² Departments of Medicine and Genetics, Case Comprehensive Cancer Center, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH, USA.
¹⁵³ Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, The Netherlands.
¹⁵⁴ Division of Human Nutrition, Wageningen University and Research, Wageningen, The Netherlands.
¹⁵⁵ Genomic Medicine Group, Galician Public Foundation of Genomic Medicine, Servicio Galego de Saude, Santiago de Compostela, Spain.
¹⁵⁶ Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago de Compostela, Spain.
¹⁵⁷ Italian Institute for Genomic Medicine, Candiolo Cancer Institute FPO-IRCCS, Candiolo (TO), Italy.
¹⁵⁸ Candiolo Cancer Institute FPO-IRCCS, Candiolo (TO), Italy.
¹⁵⁹ Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
¹⁶⁰ National University Cancer Institute, Singapore, Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
¹⁶¹ Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
¹⁶² Cancer Immunology Program, Dana-Farber Harvard Cancer Center, Boston, MA, USA.
¹⁶³ Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁶⁴ Department of Biostatistics, University of Washington, Seattle, WA, USA.
¹⁶⁵ Service de Génétique Médicale, Centre Hospitalier Universitaire Nantes, Nantes, France.
¹⁶⁶ SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
¹⁶⁷ Department of Pediatrics, Nationwide Children's Hospital, The Steve and Cindy Rasmussen Institute for Genomic Medicine, Columbus, OH, USA.
¹⁶⁸ Division of Epidemiology, National Cancer Center Institute for Cancer Control, National Cancer Center, Tokyo, Japan.
¹⁶⁹ Division of Cohort Research, National Cancer Center Institute for Cancer Control, National Cancer Center, Tokyo, Japan.
¹⁷⁰ Department of Preventive Medicine, Center for Genetic Epidemiology, University of Southern California, Los Angeles, CA, USA.
¹⁷¹ Cancer Center, University of Hawaii, Honolulu, HI, USA.
¹⁷² Preventative Medicine, University of Southern California, Los Angeles, CA, USA.
¹⁷³ USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
¹⁷⁴ Van Andel Research Institute, Grand Rapids, MI, USA.
¹⁷⁵ MRC Human Genetics Unit, Institute of Genomics and Cancer, University of Edinburgh, Edinburgh, UK.
¹⁷⁶ Lothian Birth Cohorts group, Department of Psychology, University of Edinburgh, Edinburgh, UK.
¹⁷⁷ Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, UK.
¹⁷⁸ Department of Pathology, National University Hospital, National University Health System, Singapore, Singapore.
¹⁷⁹ Edinburgh Cancer Research Centre, Institute of Genomics and Cancer, University of Edinburgh, Edinburgh, UK. Ian.Tomlinson@ed.ac.uk.
¹⁸⁰ Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK. Ian.Tomlinson@ed.ac.uk.
¹⁸¹ Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA. wei.zheng@vanderbilt.edu.
¹⁸² Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK. malcolm.dunlop@ed.ac.uk.
¹⁸³ Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK. Richard.Houlston@icr.ac.uk.
¹⁸⁴ Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. upeters@fredhutch.org.
¹⁸⁵ Department of Epidemiology, University of Washington, Seattle, WA, USA. upeters@fredhutch.org.

^# Contributed equally.

PMID: 36539618
PMCID: PMC10094749
DOI: 10.1038/s41588-022-01222-9

Meta-Analysis

Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries

Ceres Fernandez-Rozadilla et al. Nat Genet. 2023 Jan.

. 2023 Jan;55(1):89-99.

doi: 10.1038/s41588-022-01222-9. Epub 2022 Dec 20.

Authors

Affiliations

¹ Edinburgh Cancer Research Centre, Institute of Genomics and Cancer, University of Edinburgh, Edinburgh, UK.
² Genomic Medicine Group, Instituto de Investigacion Sanitaria de Santiago, Santiago de Compostela, Spain.
³ Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
⁴ Danish Institute for Advanced Study, Department of Public Health, University of Southern Denmark, Odense, Denmark.
⁵ Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA.
⁶ Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK.
⁷ Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
⁸ Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.
⁹ Population and Cancer Prevention Program, Case Comprehensive Cancer Center, Cleveland, OH, USA.
¹⁰ Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute, Barcelona, Spain.
¹¹ Oncology Data Analytics Program, Catalan Institute of Oncology, Barcelona, Spain.
¹² Consortium for Biomedical Research in Epidemiology and Public Health, Madrid, Madrid, Spain.
¹³ Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
¹⁴ Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, USA.
¹⁵ Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
¹⁶ Department of Public Health, Richard Doll Building, University of Oxford, Oxford, UK.
¹⁷ Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN, USA.
¹⁸ Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
¹⁹ Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
²⁰ Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
²¹ Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.
²² The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
²³ Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel.
²⁴ Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
²⁵ Clalit National Cancer Control Center, Haifa, Israel.
²⁶ Consortium for Biomedical Research in Epidemiology and Public Health, Madrid, Spain.
²⁷ Biomedicine Institute, University of León, León, Spain.
²⁸ Center for Colorectal Cancer, National Cancer Center Hospital, National Cancer Center, Gyeonggi-do, South Korea.
²⁹ Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Gyeonggi-do, South Korea.
³⁰ Department of Epidemiology and Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, South Korea.
³¹ Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, South Korea.
³² Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, South Korea.
³³ Cancer Research Institute, Seoul National University, Seoul, South Korea.
³⁴ Department of Social and Preventive Medicine, Hallym University College of Medicine, Okcheon-dong, South Korea.
³⁵ Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
³⁶ Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, Nagoya, Japan.
³⁷ Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
³⁸ Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan.
³⁹ Laboratory of Genome Technology, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
⁴⁰ School of Public Health, Sun Yat-sen University, Guangzhou, China.
⁴¹ State Key Laboratory of Oncogenes and Related Genes and Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
⁴² State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
⁴³ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia.
⁴⁴ Department of Epidemiology, School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, South Korea.
⁴⁵ Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
⁴⁶ Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁴⁷ Division of Oncology, Department of Medicine, Cedars-Sinai Cancer Research Center for Health Equity, Los Angeles, CA, USA.
⁴⁸ Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
⁴⁹ Division of Biomedical Sciences, Memorial University of Newfoundland, St. John, Ontario, Canada.
⁵⁰ School of Public Health, University of Washington, Seattle, WA, USA.
⁵¹ City of Hope National Medical Center, Translational Genomics Research Institute, Phoenix, AZ, USA.
⁵² Institute of Medical Genetics, Cardiff University, Cardiff, UK.
⁵³ MRC Clinical Trials Unit, Medical Research Council, Cardiff, UK.
⁵⁴ MRC Institute for Radiation Oncology, University of Oxford, Oxford, UK.
⁵⁵ Department of Oncology, University of Oxford, Oxford, UK.
⁵⁶ Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
⁵⁷ Department of Surgical Oncology, University Hospital for Tumors, Sestre milosrdnice University Hospital Center, Zagreb, Croatia.
⁵⁸ Department of Pathology, Central Finland Health Care District, Jyväskylä, Finland.
⁵⁹ Central Finland Health Care District, Jyväskylä, Finland.
⁶⁰ Department of Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland.
⁶¹ Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland.
⁶² Genome-Scale Biology Research Program, University of Helsinki, Helsinki, Finland.
⁶³ Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Finland.
⁶⁴ Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland.
⁶⁵ Faculty of Social Sciences, Tampere University, Tampere, Finland.
⁶⁶ Folkhälsan Research Centre, University of Helsinki, Helsinki, Finland.
⁶⁷ Human Potential Translational Research Programme, National University of Singapore, Singapore, Singapore.
⁶⁸ Unit of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
⁶⁹ Department of Surgery, Abdominal Centre, Helsinki University Hospital, Helsinki, Finland.
⁷⁰ Department of Oncology, University of Toronto, Toronto, Ontario, Canada.
⁷¹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
⁷² Department of Nutritional Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
⁷³ Slone Epidemiology Center at Boston University, Boston, MA, USA.
⁷⁴ Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
⁷⁵ Colorectal Oncogenomics Group, Department of Clinical Pathology, University of Melbourne, Parkville, Victoria, Australia.
⁷⁶ University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, Victoria, Australia.
⁷⁷ Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Victoria, Australia.
⁷⁸ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁷⁹ Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA.
⁸⁰ Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
⁸¹ Institute of Cancer Research, Department of Medicine I, Medical University Vienna, Vienna, Austria.
⁸² Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY, USA.
⁸³ Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
⁸⁴ University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg, Hamburg, Germany.
⁸⁵ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
⁸⁶ Division of Preventive Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany.
⁸⁷ German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany.
⁸⁸ Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.
⁸⁹ Research Centre for Hauora and Health, Massey University, Wellington, New Zealand.
⁹⁰ Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
⁹¹ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
⁹² Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
⁹³ Institute of Nutritional Science, University of Potsdam, Potsdam, Germany.
⁹⁴ Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.
⁹⁵ Gastroenterology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, University of Barcelona, Barcelona, Spain.
⁹⁶ Department of Genetics, Stanford University, Stanford, CA, USA.
⁹⁷ Department of Population and Public Health Sciences, USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁹⁸ Jeonnam Regional Cancer Center, Chonnam National University Hwasun Hospital, Hwasun, South Korea.
⁹⁹ Bioinformatics and Data Science Research Center, Bina Nusantara University, Jakarta, Indonesia.
¹⁰⁰ Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.
¹⁰¹ Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
¹⁰² Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
¹⁰³ Department of Clinical Pathology, University of Melbourne, Melbourne, Victoria, Australia.
¹⁰⁴ Department of Medical Oncology and Center For Precision Medicine, City of Hope National Medical Center, Duarte, CA, USA.
¹⁰⁵ Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
¹⁰⁶ Clalit Health Services, Personalized Genomic Service, Lady Davis Carmel Medical Center, Haifa, Israel.
¹⁰⁷ Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
¹⁰⁸ Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
¹⁰⁹ Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
¹¹⁰ Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA.
¹¹¹ Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden.
¹¹² Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden.
¹¹³ Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
¹¹⁴ Division of Human Genetics, Department of Internal Medicine, Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
¹¹⁵ Division of Epidemiology, Department of Population Health, New York University School of Medicine, New York, NY, USA.
¹¹⁶ Population Sciences, Disparities and Community Engagement, University of California San Diego Moores Cancer Center, La Jolla, CA, USA.
¹¹⁷ Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA.
¹¹⁸ Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
¹¹⁹ Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
¹²⁰ Department of Gastroenterology, Kaiser Permanente Medical Center, San Francisco, CA, USA.
¹²¹ Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
¹²² Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
¹²³ Taipei Medical University, Taipei, Taiwan.
¹²⁴ Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
¹²⁵ Department of Epidemiology, University of Washington School of Public Health, Seattle, WA, USA.
¹²⁶ Center for Inherited Disease Research, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹²⁷ Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
¹²⁸ Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
¹²⁹ Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
¹³⁰ Broad Institute of Harvard and MIT, Cambridge, MA, USA.
¹³¹ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
¹³² Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
¹³³ Comprehensive Cancer Center, University of Puerto Rico, San Juan, Puerto Rico.
¹³⁴ Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
¹³⁵ Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
¹³⁶ Nuffield Department of Population Health, University of Oxford, Oxford, UK.
¹³⁷ Department of General Surgery, University Hospital Rostock, Rostock, Germany.
¹³⁸ Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA.
¹³⁹ Department of Computer Science, Stanford University, Stanford, CA, USA.
¹⁴⁰ Department of Genome Sciences, University of Washington, Seattle, WA, USA.
¹⁴¹ Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
¹⁴² Department of Medicine I, University Hospital Dresden, Technische Universität Dresden, Dresden, Germany.
¹⁴³ Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
¹⁴⁴ Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic.
¹⁴⁵ Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic.
¹⁴⁶ Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic.
¹⁴⁷ Department of Oncology Ludwig Center at the Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁴⁸ Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁴⁹ Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
¹⁵⁰ Department of Surgery, University of Tennessee Health Science Center, Memphis, TN, USA.
¹⁵¹ Departments of Cancer Biology and Genetics and Internal Medicine, Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA.
¹⁵² Departments of Medicine and Genetics, Case Comprehensive Cancer Center, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH, USA.
¹⁵³ Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, The Netherlands.
¹⁵⁴ Division of Human Nutrition, Wageningen University and Research, Wageningen, The Netherlands.
¹⁵⁵ Genomic Medicine Group, Galician Public Foundation of Genomic Medicine, Servicio Galego de Saude, Santiago de Compostela, Spain.
¹⁵⁶ Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago de Compostela, Spain.
¹⁵⁷ Italian Institute for Genomic Medicine, Candiolo Cancer Institute FPO-IRCCS, Candiolo (TO), Italy.
¹⁵⁸ Candiolo Cancer Institute FPO-IRCCS, Candiolo (TO), Italy.
¹⁵⁹ Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
¹⁶⁰ National University Cancer Institute, Singapore, Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
¹⁶¹ Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
¹⁶² Cancer Immunology Program, Dana-Farber Harvard Cancer Center, Boston, MA, USA.
¹⁶³ Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁶⁴ Department of Biostatistics, University of Washington, Seattle, WA, USA.
¹⁶⁵ Service de Génétique Médicale, Centre Hospitalier Universitaire Nantes, Nantes, France.
¹⁶⁶ SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
¹⁶⁷ Department of Pediatrics, Nationwide Children's Hospital, The Steve and Cindy Rasmussen Institute for Genomic Medicine, Columbus, OH, USA.
¹⁶⁸ Division of Epidemiology, National Cancer Center Institute for Cancer Control, National Cancer Center, Tokyo, Japan.
¹⁶⁹ Division of Cohort Research, National Cancer Center Institute for Cancer Control, National Cancer Center, Tokyo, Japan.
¹⁷⁰ Department of Preventive Medicine, Center for Genetic Epidemiology, University of Southern California, Los Angeles, CA, USA.
¹⁷¹ Cancer Center, University of Hawaii, Honolulu, HI, USA.
¹⁷² Preventative Medicine, University of Southern California, Los Angeles, CA, USA.
¹⁷³ USC Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
¹⁷⁴ Van Andel Research Institute, Grand Rapids, MI, USA.
¹⁷⁵ MRC Human Genetics Unit, Institute of Genomics and Cancer, University of Edinburgh, Edinburgh, UK.
¹⁷⁶ Lothian Birth Cohorts group, Department of Psychology, University of Edinburgh, Edinburgh, UK.
¹⁷⁷ Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, UK.
¹⁷⁸ Department of Pathology, National University Hospital, National University Health System, Singapore, Singapore.
¹⁷⁹ Edinburgh Cancer Research Centre, Institute of Genomics and Cancer, University of Edinburgh, Edinburgh, UK. Ian.Tomlinson@ed.ac.uk.
¹⁸⁰ Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK. Ian.Tomlinson@ed.ac.uk.
¹⁸¹ Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA. wei.zheng@vanderbilt.edu.
¹⁸² Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK. malcolm.dunlop@ed.ac.uk.
¹⁸³ Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK. Richard.Houlston@icr.ac.uk.
¹⁸⁴ Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. upeters@fredhutch.org.
¹⁸⁵ Department of Epidemiology, University of Washington, Seattle, WA, USA. upeters@fredhutch.org.

^# Contributed equally.

PMID: 36539618
PMCID: PMC10094749
DOI: 10.1038/s41588-022-01222-9

Erratum in

Author Correction: Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries.
Fernandez-Rozadilla C, Timofeeva M, Chen Z, Law P, Thomas M, Schmit S, Díez-Obrero V, Hsu L, Fernandez-Tajes J, Palles C, Sherwood K, Briggs S, Svinti V, Donnelly K, Farrington S, Blackmur J, Vaughan-Shaw P, Shu XO, Long J, Cai Q, Guo X, Lu Y, Broderick P, Studd J, Huyghe J, Harrison T, Conti D, Dampier C, Devall M, Schumacher F, Melas M, Rennert G, Obón-Santacana M, Martín-Sánchez V, Moratalla-Navarro F, Oh JH, Kim J, Jee SH, Jung KJ, Kweon SS, Shin MH, Shin A, Ahn YO, Kim DH, Oze I, Wen W, Matsuo K, Matsuda K, Tanikawa C, Ren Z, Gao YT, Jia WH, Hopper J, Jenkins M, Win AK, Pai R, Figueiredo J, Haile R, Gallinger S, Woods M, Newcomb P, Duggan D, Cheadle J, Kaplan R, Maughan T, Kerr R, Kerr D, Kirac I, Böhm J, Mecklin LP, Jousilahti P, Knekt P, Aaltonen L, Rissanen H, Pukkala E, Eriksson J, Cajuso T, Hänninen U, Kondelin J, Palin K, Tanskanen T, Renkonen-Sinisalo L, Zanke B, Männistö S, Albanes D, Weinstein S, Ruiz-Narvaez E, Palmer J, Buchanan D, Platz E, Visvanathan K, Ulrich C, Siegel E, Brezina S, Gsur A, Campbell P, Chang-Claude J, Hoffmeister M, Brenner H, Slattery M, Potter J, Tsilidis K, Schulze M, Gunter M, Murphy N, Castells A, Castellví-Bel S, Moreira L, Arndt V, Shcher… See abstract for full author list ➔ Fernandez-Rozadilla C, et al. Nat Genet. 2023 Mar;55(3):519-520. doi: 10.1038/s41588-023-01334-w. Nat Genet. 2023. PMID: 36782065 No abstract available.

Abstract

Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.

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Conflict of interest statement

Competing interests

AC is consultant to Bayer Pharma AG, Boehringer Ingelheim, and Pfizer Inc. for work unrelated to this manuscript; AS is an employee at Insitro, incl. consulting fees from BMS; HH is SAB for Invitae Genetics, Promega, and Genome Medical. Stock/Stock options for Genome Medical and GI OnDemand; JK is a consultant for Guardant Health; NP is a collaborator for Thrive and Exact, PGDx, CAGE, NeoPhore, Vidium, ManaTbio, and receives royalties for licensed technologies according to JHU rules; RKP collaborates with Eli Lilly, AbbVie, Allergan, Verily, and Alimentiv, which include consulting fees (outside of the submitted work); SAB has financial interest in Adaptive Biotechnologies; SBG is co-founder, Brogent International LLC; TSM receives research and honoraria from Merck Serono; ZKS’s immediate family member serves as a consultant in Ophthalmology for Alcon, Adverum, Gyroscope Therapeutics Limited, Neurogene, and RegenexBio (outside the submitted work). VM has research projects and owns stocks of Aniling. The remaining authors declare no competing interests.

Figures

**Figure 1.. Summary of the study data and analytical design, and the number of previously unreported CRC risk loci discovered.**
The figure illustrates the information for the different analyses used: GWAS (green), TWAS (blue), MWAS (yellow) used to identify additional risk loci. These are later used to select credible effector genes annotated to functions and tissues.

**Figure 2.. Effector genes for CRC risk and the cellular processes in which they act.**
Pie chart describing the proportion and list of effector genes allocated to each process.

**Figure 3.. Representation of effector genes and their putative actions in the colorectum.**
Diagram representing the processes that the combined GWAS, TWAS and MWAS analyses have unveiled as relevant to CRC risk. Exemplar effector genes from cellular processes and pathways (in capitals) are chosen to depict each category.

See this image and copyright information in PMC

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Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries

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Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries

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