. 2023 Oct 2;14(1):6147.

doi: 10.1038/s41467-023-41819-0.

Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations

Minta Thomas¹, Yu-Ru Su^{1

2}, Elisabeth A Rosenthal³, Lori C Sakoda^{1

4}, Stephanie L Schmit^{5

6}, Maria N Timofeeva^{7

8}, Zhishan Chen⁹, Ceres Fernandez-Rozadilla^{10

11}, Philip J Law¹², Neil Murphy¹³, Robert Carreras-Torres¹⁴, Virginia Diez-Obrero^{15

16

17}, Franzel J B van Duijnhoven¹⁸, Shangqing Jiang¹, Aesun Shin¹⁹, Alicja Wolk²⁰, Amanda I Phipps^{1

21}, Andrea Burnett-Hartman²², Andrea Gsur²³, Andrew T Chan^{24

25

26

27

28

29}, Ann G Zauber³⁰, Anna H Wu³¹, Annika Lindblom^{32

33}, Caroline Y Um³⁴, Catherine M Tangen³⁵, Chris Gignoux³⁶, Christina Newton³⁴, Christopher A Haiman³⁷, Conghui Qu¹, D Timothy Bishop³⁸, Daniel D Buchanan^{39

40

41}, David R Crosslin⁴², David V Conti³⁷, Dong-Hyun Kim⁴³, Elizabeth Hauser^{44

45}, Emily White^{1

46}, Erin Siegel⁴⁷, Fredrick R Schumacher⁴⁸, Gad Rennert^{49

50}, Graham G Giles⁵¹, Heather Hampel⁵², Hermann Brenner^{53

54}, Isao Oze⁵⁵, Jae Hwan Oh⁵⁶, Jeffrey K Lee^{57

58}, Jennifer L Schneider⁴, Jenny Chang-Claude^{59

60}, Jeongseon Kim⁶¹, Jeroen R Huyghe¹, Jiayin Zheng¹, Jochen Hampe⁶², Joel Greenson⁵⁸, John L Hopper^{63

64}, Julie R Palmer⁶⁵, Kala Visvanathan⁶⁶, Keitaro Matsuo⁶⁷, Koichi Matsuda⁶⁸, Keum Ji Jung⁶⁹, Li Li⁷⁰, Loic Le Marchand⁷¹, Ludmila Vodickova^{72

73

74}, Luis Bujanda⁷⁵, Marc J Gunter¹³, Marco Matejcic⁷⁶, Mark A Jenkins^{40

63}, Martha L Slattery⁷⁷, Mauro D'Amato^{78

79}, Meilin Wang⁸⁰, Michael Hoffmeister⁵³, Michael O Woods⁸¹, Michelle Kim¹, Mingyang Song^{24

26

82}, Motoki Iwasaki^{83

84}, Mulong Du^{85

86}, Natalia Udaltsova⁴, Norie Sawada⁸⁴, Pavel Vodicka^{72

73}, Peter T Campbell⁸⁷, Polly A Newcomb¹, Qiuyin Cai⁹, Rachel Pearlman⁵², Rish K Pai⁸⁸, Robert E Schoen⁸⁹, Robert S Steinfelder¹, Robert W Haile⁹⁰, Rosita Vandenputtelaar⁹¹, Ross L Prentice¹, Sébastien Küry⁹², Sergi Castellví-Bel⁹³, Shoichiro Tsugane⁸⁴, Sonja I Berndt⁹⁴, Soo Chin Lee⁹⁵, Stefanie Brezina²³, Stephanie J Weinstein⁹⁴, Stephen J Chanock⁹⁴, Sun Ha Jee⁹⁶, Sun-Seog Kweon^{97

98}, Susan Vadaparampil⁸², Tabitha A Harrison¹, Taiki Yamaji⁸³, Temitope O Keku⁹⁹, Veronika Vymetalkova^{72

73}, Volker Arndt⁵³, Wei-Hua Jia¹⁰⁰, Xiao-Ou Shu¹⁰¹, Yi Lin¹, Yoon-Ok Ahn¹⁹, Zsofia K Stadler¹⁰², Bethany Van Guelpen^{103

104}, Cornelia M Ulrich¹⁰⁵, Elizabeth A Platz⁶⁶, John D Potter¹, Christopher I Li¹, Reinier Meester⁹¹, Victor Moreno^{106

107

108

109}, Jane C Figueiredo^{37

110}, Graham Casey¹¹¹, Iris Lansdorp Vogelaar⁹¹, Malcolm G Dunlop⁸, Stephen B Gruber¹¹², Richard B Hayes¹¹³, Paul D P Pharoah¹¹⁴, Richard S Houlston¹², Gail P Jarvik³, Ian P Tomlinson¹¹, Wei Zheng⁹, Douglas A Corley^{4

115}, Ulrike Peters^{116

117}, Li Hsu^{118

119}

Affiliations

¹ Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
² Biostatistics Division, Kaiser Permanente Washington Health Research Institute, Seattle, USA.
³ Department of Medicine (Medical Genetics), University of Washington Medical Center, Seattle, WA, 98195, USA.
⁴ Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
⁵ Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.
⁶ Population and Cancer Prevention Program, Case Comprehensive Cancer Center, Cleveland, USA.
⁷ Danish Institute for Advanced Study (DIAS), Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark.
⁸ Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, U, Germany.
⁹ Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁰ Instituto de Investigacion Sanitaria de Santiago (IDIS), Choupana sn, 15706, Santiago de Compostela, Spain.
¹¹ Edinburgh Cancer Research Centre, Institute of Genomics and Cancer, University of Edinburgh, Crewe Road, Edinburgh, EH4 2XU, UK.
¹² Division of Genetics and Epidemiology, The Institute of Cancer Reseach, London, SW7 3RP, UK.
¹³ Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.
¹⁴ Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), Salt, 17190, Girona, Spain.
¹⁵ Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program, Catalan Institute of Oncology, Barcelona, 08908, Spain.
¹⁶ Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute, Barcelona, 08908, Spain.
¹⁷ Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, 08908, Spain.
¹⁸ Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands.
¹⁹ Department of Preventive Medicine, Seoul National University College of Medicine, Seoul National University Cancer Research Institute, Seoul, South Korea.
²⁰ Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
²¹ Department of Epidemiology, University of Washington, Seattle, WA, USA.
²² Institute for Health Research, Kaiser Permanente Colorado, Denver, CO, USA.
²³ .Center for Cancer Research, Medical University Vienna, Vienna, Austria.
²⁴ Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
²⁵ Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
²⁶ Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
²⁷ Broad Institute of Harvard and MIT, Cambridge, MA, USA.
²⁸ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
²⁹ Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
³⁰ Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
³¹ University of Southern California, Preventative Medicine, Los Angeles, CA, USA.
³² Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
³³ Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
³⁴ Department of Population Science, American Cancer Society, Atlanta, GA, USA.
³⁵ SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
³⁶ Colorado Center for Personalized Medicine, University of Colorado - Anschutz Medical Campus, Aurora, CO, USA.
³⁷ Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
³⁸ Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
³⁹ Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, VIC, 3000, Australia.
⁴⁰ University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC, 3000, Australia.
⁴¹ Genomic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, VIC, 3000, Australia.
⁴² Department of Bioinformatics and Medical Education, University of Washington Medical Center, Seattle, WA, 98195, USA.
⁴³ Department of Social and Preventive Medicine, Hallym University College of Medicine, Okcheon-dong, South Korea.
⁴⁴ VA Cooperative Studies Program Epidemiology Center, Durham Veterans Affairs Health Care System, Durham, NC, USA.
⁴⁵ Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.
⁴⁶ Department of Epidemiology, University of Washington School of Public Health, Seattle, WA, USA.
⁴⁷ Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
⁴⁸ Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
⁴⁹ Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel.
⁵⁰ Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
⁵¹ Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia.
⁵² Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
⁵³ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁵⁴ Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
⁵⁵ .Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
⁵⁶ .Research Institute and Hospital, National Cancer Center, Goyang, South Korea, South Korea.
⁵⁷ .Department of Gastroenterology, Kaiser Permanente San Francisco Medical Center, San Francisco, CA, USA.
⁵⁸ Department of Pathology, University of Michigan, Ann Arbor, MI, 48104, USA.
⁵⁹ Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁶⁰ University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany.
⁶¹ Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Gyeonggi-do, South Korea.
⁶² Department of Medicine I, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany.
⁶³ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
⁶⁴ Department of Epidemiology, School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, South Korea.
⁶⁵ Slone Epidemiology Center, School of Medicine, Boston University, Boston, MA, USA.
⁶⁶ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁶⁷ Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, Nagoya, Japan.
⁶⁸ Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan.
⁶⁹ Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea.
⁷⁰ Department of Family Medicine, University of Virginia, Charlottesville, VA, USA.
⁷¹ University of Hawaii Cancer Center, Honolulu, HI, USA.
⁷² Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic.
⁷³ Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic.
⁷⁴ Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic.
⁷⁵ Department of Gastroenterology, Biodonostia Health Research Institute, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universidad del País Vasco (UPV/EHU), San Sebastián, Spain.
⁷⁶ Moffitt Cancer Center, Tampa, FL, USA.
⁷⁷ Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.
⁷⁸ Department of Medicine and Surgery, LUM University, Camassima, Italy.
⁷⁹ Gastrointestinal Genetics Lab, CIC bioGUNE-BRTA, Derio, Spain.
⁸⁰ Department of Environmental Genomics, School of Public Health, Nanjing Medical University, Nanjing, China.
⁸¹ Memorial University of Newfoundland, Discipline of Genetics, St. John's, Canada.
⁸² Departments of Epidemiology and Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA.
⁸³ Division of Epidemiology, National Cancer Center Institute for Cancer Control, National Cancer Center, Tokyo, Japan.
⁸⁴ Division of Cohort Research, National Cancer Center Institute for Cancer Control, National Cancer Center, Tokyo, Japan.
⁸⁵ Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
⁸⁶ Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁸⁷ Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
⁸⁸ Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
⁸⁹ Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
⁹⁰ Samuel Oschin Comprehensive Cancer Institute, CEDARS-SINAI, Los Angeles, CA, USA.
⁹¹ Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁹² Nantes Université, CHU Nantes, Service de Génétique Médicale, F-44000, Nantes, France.
⁹³ Gastroenterology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain.
⁹⁴ Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
⁹⁵ National University Cancer Institute, Singapore, Singapore.
⁹⁶ Department of Epidemiology and Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea.
⁹⁷ Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Korea.
⁹⁸ Jeonnam Regional Cancer Center, Chonnam National University Hwasun Hospital, Hwasun, Korea.
⁹⁹ Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA.
¹⁰⁰ State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
¹⁰¹ Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁰² Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹⁰³ Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden.
¹⁰⁴ Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden.
¹⁰⁵ Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA.
¹⁰⁶ Oncology Data Analytics Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
¹⁰⁷ CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
¹⁰⁸ Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
¹⁰⁹ ONCOBEL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
¹¹⁰ Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
¹¹¹ Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
¹¹² Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA.
¹¹³ Division of Epidemiology, Department of Population Health, New York University School of Medicine, New York, NY, USA.
¹¹⁴ Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
¹¹⁵ Department of Gastroenterology, Kaiser Permanente Medical Center, San Francisco, CA, USA.
¹¹⁶ Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA. upeters@fredhutch.org.
¹¹⁷ Department of Epidemiology, University of Washington, Seattle, WA, USA. upeters@fredhutch.org.
¹¹⁸ Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA. lih@fredhutch.org.
¹¹⁹ Department of Biostatistics, University of Washington, Seattle, WA, USA. lih@fredhutch.org.

PMID: 37783704
PMCID: PMC10545678
DOI: 10.1038/s41467-023-41819-0

Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations

Minta Thomas et al. Nat Commun. 2023.

. 2023 Oct 2;14(1):6147.

doi: 10.1038/s41467-023-41819-0.

Authors

Affiliations

¹ Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
² Biostatistics Division, Kaiser Permanente Washington Health Research Institute, Seattle, USA.
³ Department of Medicine (Medical Genetics), University of Washington Medical Center, Seattle, WA, 98195, USA.
⁴ Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
⁵ Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.
⁶ Population and Cancer Prevention Program, Case Comprehensive Cancer Center, Cleveland, USA.
⁷ Danish Institute for Advanced Study (DIAS), Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark.
⁸ Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, U, Germany.
⁹ Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁰ Instituto de Investigacion Sanitaria de Santiago (IDIS), Choupana sn, 15706, Santiago de Compostela, Spain.
¹¹ Edinburgh Cancer Research Centre, Institute of Genomics and Cancer, University of Edinburgh, Crewe Road, Edinburgh, EH4 2XU, UK.
¹² Division of Genetics and Epidemiology, The Institute of Cancer Reseach, London, SW7 3RP, UK.
¹³ Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.
¹⁴ Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), Salt, 17190, Girona, Spain.
¹⁵ Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program, Catalan Institute of Oncology, Barcelona, 08908, Spain.
¹⁶ Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute, Barcelona, 08908, Spain.
¹⁷ Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, 08908, Spain.
¹⁸ Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands.
¹⁹ Department of Preventive Medicine, Seoul National University College of Medicine, Seoul National University Cancer Research Institute, Seoul, South Korea.
²⁰ Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
²¹ Department of Epidemiology, University of Washington, Seattle, WA, USA.
²² Institute for Health Research, Kaiser Permanente Colorado, Denver, CO, USA.
²³ .Center for Cancer Research, Medical University Vienna, Vienna, Austria.
²⁴ Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
²⁵ Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
²⁶ Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
²⁷ Broad Institute of Harvard and MIT, Cambridge, MA, USA.
²⁸ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
²⁹ Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
³⁰ Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
³¹ University of Southern California, Preventative Medicine, Los Angeles, CA, USA.
³² Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
³³ Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
³⁴ Department of Population Science, American Cancer Society, Atlanta, GA, USA.
³⁵ SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
³⁶ Colorado Center for Personalized Medicine, University of Colorado - Anschutz Medical Campus, Aurora, CO, USA.
³⁷ Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
³⁸ Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
³⁹ Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, VIC, 3000, Australia.
⁴⁰ University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC, 3000, Australia.
⁴¹ Genomic Medicine and Family Cancer Clinic, The Royal Melbourne Hospital, Parkville, VIC, 3000, Australia.
⁴² Department of Bioinformatics and Medical Education, University of Washington Medical Center, Seattle, WA, 98195, USA.
⁴³ Department of Social and Preventive Medicine, Hallym University College of Medicine, Okcheon-dong, South Korea.
⁴⁴ VA Cooperative Studies Program Epidemiology Center, Durham Veterans Affairs Health Care System, Durham, NC, USA.
⁴⁵ Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.
⁴⁶ Department of Epidemiology, University of Washington School of Public Health, Seattle, WA, USA.
⁴⁷ Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
⁴⁸ Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
⁴⁹ Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel.
⁵⁰ Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
⁵¹ Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia.
⁵² Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
⁵³ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁵⁴ Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.
⁵⁵ .Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
⁵⁶ .Research Institute and Hospital, National Cancer Center, Goyang, South Korea, South Korea.
⁵⁷ .Department of Gastroenterology, Kaiser Permanente San Francisco Medical Center, San Francisco, CA, USA.
⁵⁸ Department of Pathology, University of Michigan, Ann Arbor, MI, 48104, USA.
⁵⁹ Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁶⁰ University Medical Centre Hamburg-Eppendorf, University Cancer Centre Hamburg (UCCH), Hamburg, Germany.
⁶¹ Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Gyeonggi-do, South Korea.
⁶² Department of Medicine I, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany.
⁶³ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
⁶⁴ Department of Epidemiology, School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, South Korea.
⁶⁵ Slone Epidemiology Center, School of Medicine, Boston University, Boston, MA, USA.
⁶⁶ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁶⁷ Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, Nagoya, Japan.
⁶⁸ Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan.
⁶⁹ Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea.
⁷⁰ Department of Family Medicine, University of Virginia, Charlottesville, VA, USA.
⁷¹ University of Hawaii Cancer Center, Honolulu, HI, USA.
⁷² Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic.
⁷³ Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic.
⁷⁴ Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic.
⁷⁵ Department of Gastroenterology, Biodonostia Health Research Institute, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universidad del País Vasco (UPV/EHU), San Sebastián, Spain.
⁷⁶ Moffitt Cancer Center, Tampa, FL, USA.
⁷⁷ Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.
⁷⁸ Department of Medicine and Surgery, LUM University, Camassima, Italy.
⁷⁹ Gastrointestinal Genetics Lab, CIC bioGUNE-BRTA, Derio, Spain.
⁸⁰ Department of Environmental Genomics, School of Public Health, Nanjing Medical University, Nanjing, China.
⁸¹ Memorial University of Newfoundland, Discipline of Genetics, St. John's, Canada.
⁸² Departments of Epidemiology and Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA.
⁸³ Division of Epidemiology, National Cancer Center Institute for Cancer Control, National Cancer Center, Tokyo, Japan.
⁸⁴ Division of Cohort Research, National Cancer Center Institute for Cancer Control, National Cancer Center, Tokyo, Japan.
⁸⁵ Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
⁸⁶ Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁸⁷ Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
⁸⁸ Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
⁸⁹ Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
⁹⁰ Samuel Oschin Comprehensive Cancer Institute, CEDARS-SINAI, Los Angeles, CA, USA.
⁹¹ Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁹² Nantes Université, CHU Nantes, Service de Génétique Médicale, F-44000, Nantes, France.
⁹³ Gastroenterology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain.
⁹⁴ Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
⁹⁵ National University Cancer Institute, Singapore, Singapore.
⁹⁶ Department of Epidemiology and Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea.
⁹⁷ Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Korea.
⁹⁸ Jeonnam Regional Cancer Center, Chonnam National University Hwasun Hospital, Hwasun, Korea.
⁹⁹ Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA.
¹⁰⁰ State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
¹⁰¹ Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁰² Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
¹⁰³ Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden.
¹⁰⁴ Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden.
¹⁰⁵ Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA.
¹⁰⁶ Oncology Data Analytics Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
¹⁰⁷ CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
¹⁰⁸ Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
¹⁰⁹ ONCOBEL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
¹¹⁰ Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
¹¹¹ Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
¹¹² Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA.
¹¹³ Division of Epidemiology, Department of Population Health, New York University School of Medicine, New York, NY, USA.
¹¹⁴ Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
¹¹⁵ Department of Gastroenterology, Kaiser Permanente Medical Center, San Francisco, CA, USA.
¹¹⁶ Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA. upeters@fredhutch.org.
¹¹⁷ Department of Epidemiology, University of Washington, Seattle, WA, USA. upeters@fredhutch.org.
¹¹⁸ Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA. lih@fredhutch.org.
¹¹⁹ Department of Biostatistics, University of Washington, Seattle, WA, USA. lih@fredhutch.org.

PMID: 37783704
PMCID: PMC10545678
DOI: 10.1038/s41467-023-41819-0

Abstract

Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice.

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Conflict of interest statement

D.A.C. receives funds from NCI. K.V. receives related Research support from Cepheid and non-financial collaboration with Optra Health. L.B. is a consultant or has received research funding from Ikan Biotech. R.E.S. got research support from Immunovia, Freenome, Exact Sciences. Z.K.S.’s immediate family member serves as a consultant in Ophthalmology for Adverum, Genentech, Gyroscope Therapeutics Limited, Neurogene, Optos Plc, Outlook Therapeutics, RegenexBio, and Regeneron (outside the submitted work). The remaining authors declare no competing interests.

Figures

**Fig. 1. Distribution of PRS.**
A PRS distributions varied across racial/ethnic groups, B PRS distribution after ancestry adjustment, C Additional mean adjustment for the Asian MG (Minor GWAS Japanese Study) study that has a different imputation panel, and D forest plot by racial and ethnic group for OR estimates +/−1.96 standard error of PRS per SD using N = 120,25; 9756; 10,377 and 80,542 of unrelated samples of Asian, Black or African American (AA), Hispanic and non-Hispanic White, respectively. The p-values in the table are two-sided. PRS is based on single cross-ancestry Asian-European PRS.

**Fig. 2. Relative Risk Estimation.**
The relative risk of individuals at different percentiles of the single cross-ancestral Asian-European PRS compared to a population average odds ratio, stratified by race and ethnicity.

**Fig. 3. Relative Risk Calibration of PRS.**
The relative risk calibration of PRS, stratified by race and ethnicity, using N = 120,25; 9756; 10,377 and 80,542 of unrelated samples of Asian, Black or AA, Hispanic and non-Hispanic White, respectively. The x-axis is the log-transformed predicted RR values and the y-axis is the log-transformed observed RR +/− 1.96 standard error with the middle bin (40–60) as the reference group.

**Fig. 4. Standardized net benefit analysis.**
a Standardized net benefit for none, all, family history (FamHx) model, and FamHx+PRS model. For the FamHx and Famhx+PRS models b true- and false-positive rates, c number of high-risk, and d number of high risk participants developed CRC at different risk thresholds, in 22,628 participants aged 40–49 from the GERA cohort.

**Fig. 5. Approaches for deriving polygenic risk scores (PRS) for colorectal cancer.**
Known Loci PRS and the details of the two different approaches for deriving PRS (1) PRS-CSx PRS and (2) LDpred PRS.

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Update of

Combining Asian-European Genome-Wide Association Studies of Colorectal Cancer Improves Risk Prediction Across Race and Ethnicity.
Thomas M, Su YR, Rosenthal EA, Sakoda LC, Schmit SL, Timofeeva MN, Chen Z, Fernandez-Rozadilla C, Law PJ, Murphy N, Carreras-Torres R, Diez-Obrero V, van Duijnhoven FJ, Jiang S, Shin A, Wolk A, Phipps AI, Burnett-Hartman A, Gsur A, Chan AT, Zauber AG, Wu AH, Lindblom A, Um CY, Tangen CM, Gignoux C, Newton C, Haiman CA, Qu C, Bishop DT, Buchanan DD, Crosslin DR, Conti DV, Kim DH, Hauser E, White E, Siegel E, Schumacher FR, Rennert G, Giles GG, Hampel H, Brenner H, Oze I, Oh JH, Lee JK, Schneider JL, Chang-Claude J, Kim J, Huyghe JR, Zheng J, Hampe J, Greenson J, Hopper JL, Palmer JR, Visvanathan K, Matsuo K, Matsuda K, Jung KJ, Li L, Marchand LL, Vodickova L, Bujanda L, Gunter MJ, Matejcic M, Jenkins MA, Slattery ML, D'Amato M, Wang M, Hoffmeister M, Woods MO, Kim M, Song M, Iwasaki M, Du M, Udaltsova N, Sawada N, Vodicka P, Campbell PT, Newcomb PA, Cai Q, Pearlman R, Pai RK, Schoen RE, Steinfelder RS, Haile RW, Vandenputtelaar R, Prentice RL, Küry S, Castellví-Bel S, Tsugane S, Berndt SI, Lee SC, Brezina S, Weinstein SJ, Chanock SJ, Jee SH, Kweon SS, Vadaparampil S, Harrison TA, Yamaji T, Keku TO, Vymetalkova V, Arndt V, Jia WH, Shu XO, Lin Y, Ahn YO, Stadler ZK, Van Guelpen B, Ul… See abstract for full author list ➔ Thomas M, et al. medRxiv [Preprint]. 2023 Jan 19:2023.01.19.23284737. doi: 10.1101/2023.01.19.23284737. medRxiv. 2023. Update in: Nat Commun. 2023 Oct 2;14(1):6147. doi: 10.1038/s41467-023-41819-0. PMID: 36789420 Free PMC article. Updated. Preprint.

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Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations

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Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations

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