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.

Biostatistics Division Kaiser Permanente Washington Health Research Institute Seattle USA

Broad Institute of Harvard and MIT Cambridge MA USA

Cancer Epidemiology Division Cancer Council Victoria Melbourne VIC Australia

Cancer Epidemiology Program H Lee Moffitt Cancer Center and Research Institute Tampa FL USA

Center for Cancer Research Medical University Vienna Vienna Austria

Center for Gastrointestinal Biology and Disease University of North Carolina Chapel Hill NC USA

Center for Public Health Genomics University of Virginia Charlottesville VA USA

Centre for Epidemiology and Biostatistics Melbourne School of Population and Global Health The University of Melbourne Melbourne VIC Australia

Channing Division of Network Medicine Brigham and Women's Hospital and Harvard Medical School Boston MA USA

CIBER Epidemiología y Salud Pública Madrid Spain

Clinical and Translational Epidemiology Unit Massachusetts General Hospital and Harvard Medical School Boston MA USA

Colon Cancer Genetics Group Medical Research Council Human Genetics Unit Institute of Genetics and Cancer University of Edinburgh Edinburgh EH4 2XU U Germany

Colorado Center for Personalized Medicine University of Colorado Anschutz Medical Campus Aurora CO USA

Colorectal Cancer Group ONCOBELL Program Bellvitge Biomedical Research Institute Barcelona 08908 Spain

Colorectal Oncogenomics Group Department of Clinical Pathology The University of Melbourne Parkville VIC 3000 Australia

Danish Institute for Advanced Study Epidemiology Biostatistics and Biodemography Department of Public Health University of Southern Denmark Odense Denmark

Department of Bioinformatics and Medical Education University of Washington Medical Center Seattle WA 98195 USA

Department of Biostatistics School of Public Health Nanjing Medical University Nanjing China

Department of Biostatistics University of Washington Seattle WA USA

Department of Cancer Biomedical Science Graduate School of Cancer Science and Policy National Cancer Center Gyeonggi do South Korea

Department of Clinical Genetics Karolinska University Hospital Stockholm Sweden

Department of Clinical Sciences Faculty of Medicine University of Barcelona Barcelona 08908 Spain

Department of Clinical Sciences Faculty of Medicine University of Barcelona Barcelona Spain

Department of Community Medicine and Epidemiology Lady Davis Carmel Medical Center Haifa Israel

Department of Environmental Genomics School of Public Health Nanjing Medical University Nanjing China

Department of Environmental Health Harvard T H Chan School of Public Health Boston MA USA

Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center New York NY USA

Department of Epidemiology and Health Promotion Graduate School of Public Health Yonsei University Seoul Korea

Department of Epidemiology and Population Health Albert Einstein College of Medicine Bronx NY USA

Department of Epidemiology Harvard T H Chan School of Public Health Harvard University Boston MA USA

Department of Epidemiology Johns Hopkins Bloomberg School of Public Health Baltimore MD USA

Department of Epidemiology School of Public Health and Institute of Health and Environment Seoul National University Seoul South Korea

Department of Epidemiology University of Washington School of Public Health Seattle WA USA

Department of Epidemiology University of Washington Seattle WA USA

Department of Family Medicine University of Virginia Charlottesville VA USA

Department of Gastroenterology Biodonostia Health Research Institute Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas San Sebastián Spain

Department of Gastroenterology Kaiser Permanente Medical Center San Francisco CA USA

Department of Gastroenterology Kaiser Permanente San Francisco Medical Center San Francisco CA USA

Department of Immunology and Infectious Diseases Harvard T H Chan School of Public Health Harvard University Boston MA USA

Department of Internal Medicine University of Utah Salt Lake City UT USA

Department of Laboratory Medicine and Pathology Mayo Clinic Arizona Scottsdale AZ USA

Department of Medical Oncology and Therapeutics Research City of Hope National Medical Center Duarte CA USA

Department of Medicine 1 University Hospital Dresden Technische Universität Dresden Dresden Germany

Department of Medicine and Epidemiology University of Pittsburgh Medical Center Pittsburgh PA USA

Department of Medicine and Surgery LUM University Camassima Italy

Department of Medicine Memorial Sloan Kettering Cancer Center New York NY USA

Department of Medicine Samuel Oschin Comprehensive Cancer Institute Cedars Sinai Medical Center Los Angeles CA USA

Department of Medicine University of Washington Medical Center Seattle WA 98195 USA

Department of Molecular Biology of Cancer Institute of Experimental Medicine of the Czech Academy of Sciences Prague Czech Republic

Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden

Department of Pathology University of Michigan Ann Arbor MI 48104 USA

Department of Population and Public Health Sciences Keck School of Medicine University of Southern California Los Angeles CA USA

Department of Population and Quantitative Health Sciences Case Western Reserve University Cleveland OH USA

Department of Population Science American Cancer Society Atlanta GA USA

Department of Preventive Medicine Chonnam National University Medical School Gwangju Korea

Department of Preventive Medicine Seoul National University College of Medicine Seoul National University Cancer Research Institute Seoul South Korea

Department of Public Health and Primary Care University of Cambridge Cambridge UK

Department of Public Health Erasmus University Medical Center Rotterdam The Netherlands

Department of Radiation Sciences Oncology Unit Umeå University Umeå Sweden

Department of Social and Preventive Medicine Hallym University College of Medicine Okcheon dong South Korea

Departments of Epidemiology and Nutrition Harvard TH Chan School of Public Health Boston MA USA

Digestive Diseases and Microbiota Group Girona Biomedical Research Institute Salt 17190 Girona Spain

Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Bethesda MD USA

Division of Cancer Epidemiology and Prevention Aichi Cancer Center Research Institute Nagoya Japan

Division of Cancer Epidemiology German Cancer Research Center Heidelberg Germany

Division of Clinical Epidemiology and Aging Research German Cancer Research Center Heidelberg Germany

Division of Cohort Research National Cancer Center Institute for Cancer Control National Cancer Center Tokyo Japan

Division of Epidemiology Department of Medicine Vanderbilt Epidemiology Center Vanderbilt University Medical Center Nashville TN USA

Division of Epidemiology Department of Population Health New York University School of Medicine New York NY USA

Division of Epidemiology National Cancer Center Institute for Cancer Control National Cancer Center Tokyo Japan

Division of Gastroenterology Massachusetts General Hospital and Harvard Medical School Boston MA USA

Division of Genetics and Epidemiology The Institute of Cancer Reseach London SW7 3RP UK

Division of Human Genetics Department of Internal Medicine The Ohio State University Comprehensive Cancer Center Columbus OH USA

Division of Human Nutrition and Health Wageningen University and Research Wageningen The Netherlands

Division of Molecular and Clinical Epidemiology Aichi Cancer Center Research Institute Nagoya Japan

Division of Preventive Oncology German Cancer Research Center Heidelberg Germany

Division of Research Kaiser Permanente Northern California Oakland CA USA

Duke Molecular Physiology Institute Duke University Medical Center Durham NC USA

Edinburgh Cancer Research Centre Institute of Genomics and Cancer University of Edinburgh Crewe Road Edinburgh EH4 2XU UK

Faculty of Medicine and Biomedical Center in Pilsen Charles University Pilsen Czech Republic

Gastroenterology Department Hospital Clínic Institut d'Investigacions Biomèdiques August Pi i Sunyer University of Barcelona Barcelona Spain

Gastrointestinal Genetics Lab CIC bioGUNE BRTA Derio Spain

Genomic Medicine and Family Cancer Clinic The Royal Melbourne Hospital Parkville VIC 3000 Australia

Genomic Medicine Institute Cleveland Clinic Cleveland OH USA

Huntsman Cancer Institute and Department of Population Health Sciences University of Utah Salt Lake City UT USA

Institute for Health Promotion Graduate School of Public Health Yonsei University Seoul Korea

Institute for Health Research Kaiser Permanente Colorado Denver CO USA

Institute of Biology and Medical Genetics 1st Faculty of Medicine Charles University Prague Czech Republic

Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden

Instituto de Investigacion Sanitaria de Santiago Choupana sn 15706 Santiago de Compostela Spain

Jeonnam Regional Cancer Center Chonnam National University Hwasun Hospital Hwasun Korea

Laboratory of Clinical Genome Sequencing Department of Computational Biology and Medical Sciences Graduate School of Frontier Sciences University of Tokyo Tokyo Japan

Leeds Institute of Cancer and Pathology University of Leeds Leeds UK

Memorial University of Newfoundland Discipline of Genetics St John's Canada

Moffitt Cancer Center Tampa FL USA

Nantes Université CHU Nantes Service de Génétique Médicale F 44000 Nantes France

National University Cancer Institute Singapore Singapore

Nutrition and Metabolism Branch International Agency for Research on Cancer World Health Organization Lyon France

ONCOBEL Program Bellvitge Biomedical Research Institute L'Hospitalet de Llobregat Barcelona Spain

Oncology Data Analytics Program Catalan Institute of Oncology IDIBELL L'Hospitalet de Llobregat Barcelona Spain

Population and Cancer Prevention Program Case Comprehensive Cancer Center Cleveland USA

Public Health Sciences Division Fred Hutchinson Cancer Center Seattle WA 98109 USA

Research Institute and Hospital National Cancer Center Goyang South Korea South Korea

Ruth and Bruce Rappaport Faculty of Medicine Technion Israel Institute of Technology Haifa Israel

Samuel Oschin Comprehensive Cancer Institute CEDARS SINAI Los Angeles CA USA

Slone Epidemiology Center School of Medicine Boston University Boston MA USA

State Key Laboratory of Oncology in South China Cancer Center Sun Yat sen University Guangzhou China

SWOG Statistical Center Fred Hutchinson Cancer Research Center Seattle WA USA

Unit of Biomarkers and Susceptibility Oncology Data Analytics Program Catalan Institute of Oncology Barcelona 08908 Spain

University Medical Centre Hamburg Eppendorf University Cancer Centre Hamburg Hamburg Germany

University of Hawaii Cancer Center Honolulu HI USA

University of Melbourne Centre for Cancer Research Victorian Comprehensive Cancer Centre Parkville VIC 3000 Australia

University of Southern California Preventative Medicine Los Angeles CA USA

VA Cooperative Studies Program Epidemiology Center Durham Veterans Affairs Health Care System Durham NC USA

Vanderbilt University Medical Center Nashville TN USA

Wallenberg Centre for Molecular Medicine Umeå University Umeå Sweden

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medRxiv. 2023 Jan 19:2023.01.19.23284737. doi: 10.1101/2023.01.19.23284737. PubMed

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