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

About this Publication
Title
Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations.
Pubmed ID
37783704 (View this publication on the PubMed website)
Digital Object Identifier
Publication
Nat Commun. 2023 Oct 2; Volume 14 (Issue 1): Pages 6147
Authors
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 FJB, Jiang S, Shin A, Wolk A, Phipps AI, Burnett-Hartman A, Gsur A, Chan AT, ...show more 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, Le Marchand L, 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, Ulrich CM, Platz EA, Potter JD, Li CI, Meester R, Moreno V, Figueiredo JC, Casey G, Lansdorp Vogelaar I, Dunlop MG, Gruber SB, Hayes RB, Pharoah PDP, Houlston RS, Jarvik GP, Tomlinson IP, Zheng W, Corley DA, Peters U, Hsu L
Affiliations
  • Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
  • Department of Medicine (Medical Genetics), University of Washington Medical Center, Seattle, WA, 98195, USA.
  • Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH, USA.
  • Danish Institute for Advanced Study (DIAS), Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark.
  • Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Instituto de Investigacion Sanitaria de Santiago (IDIS), Choupana sn, 15706, Santiago de Compostela, Spain.
  • Division of Genetics and Epidemiology, The Institute of Cancer Reseach, London, SW7 3RP, UK.
  • Nutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.
  • Digestive Diseases and Microbiota Group, Girona Biomedical Research Institute (IDIBGI), Salt, 17190, Girona, Spain.
  • Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program, Catalan Institute of Oncology, Barcelona, 08908, Spain.
...show more
  • Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands.
  • Department of Preventive Medicine, Seoul National University College of Medicine, Seoul National University Cancer Research Institute, Seoul, South Korea.
  • Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Institute for Health Research, Kaiser Permanente Colorado, Denver, CO, USA.
  • .Center for Cancer Research, Medical University Vienna, Vienna, Austria.
  • Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • University of Southern California, Preventative Medicine, Los Angeles, CA, USA.
  • Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
  • Department of Population Science, American Cancer Society, Atlanta, GA, USA.
  • SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Colorado Center for Personalized Medicine, University of Colorado - Anschutz Medical Campus, Aurora, CO, USA.
  • Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
  • Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, VIC, 3000, Australia.
  • Department of Bioinformatics and Medical Education, University of Washington Medical Center, Seattle, WA, 98195, USA.
  • Department of Social and Preventive Medicine, Hallym University College of Medicine, Okcheon-dong, South Korea.
  • VA Cooperative Studies Program Epidemiology Center, Durham Veterans Affairs Health Care System, Durham, NC, USA.
  • Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
  • Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
  • Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, Haifa, Israel.
  • Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia.
  • Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
  • Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • .Division of Cancer Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.
  • .Research Institute and Hospital, National Cancer Center, Goyang, South Korea, South Korea.
  • .Department of Gastroenterology, Kaiser Permanente San Francisco Medical Center, San Francisco, CA, USA.
  • Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA.
  • Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Gyeonggi-do, South Korea.
  • Department of Medicine I, University Hospital Dresden, Technische Universität Dresden (TU Dresden), Dresden, Germany.
  • Department of Pathology, University of Michigan, Ann Arbor, MI, 48104, USA.
  • Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
  • Slone Epidemiology Center, School of Medicine, Boston University, Boston, MA, USA.
  • Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
  • Division of Molecular and Clinical Epidemiology, Aichi Cancer Center Research Institute, Nagoya, Japan.
  • Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan.
  • Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea.
  • Department of Family Medicine, University of Virginia, Charlottesville, VA, USA.
  • University of Hawaii Cancer Center, Honolulu, HI, USA.
  • Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic.
  • 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.
  • Moffitt Cancer Center, Tampa, FL, USA.
  • University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC, 3000, Australia.
  • Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.
  • Department of Medicine and Surgery, LUM University, Camassima, Italy.
  • Department of Environmental Genomics, School of Public Health, Nanjing Medical University, Nanjing, China.
  • Memorial University of Newfoundland, Discipline of Genetics, St. John's, Canada.
  • Division of Epidemiology, National Cancer Center Institute for Cancer Control, National Cancer Center, Tokyo, Japan.
  • Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
  • Division of Cohort Research, National Cancer Center Institute for Cancer Control, National Cancer Center, Tokyo, Japan.
  • Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
  • Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Scottsdale, AZ, USA.
  • Department of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
  • Samuel Oschin Comprehensive Cancer Institute, CEDARS-SINAI, Los Angeles, CA, USA.
  • Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands.
  • Nantes Université, CHU Nantes, Service de Génétique Médicale, F-44000, Nantes, France.
  • 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.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • National University Cancer Institute, Singapore, Singapore.
  • Department of Epidemiology and Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea.
  • Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Korea.
  • Departments of Epidemiology and Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA.
  • Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA.
  • State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
  • Vanderbilt University Medical Center, Nashville, TN, USA.
  • Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Department of Radiation Sciences, Oncology Unit, Umeå University, Umeå, Sweden.
  • Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA.
  • Oncology Data Analytics Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
  • Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
  • Colon Cancer Genetics Group, Medical Research Council Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, U, Germany.
  • Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA.
  • Division of Epidemiology, Department of Population Health, New York University School of Medicine, New York, NY, USA.
  • Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Edinburgh Cancer Research Centre, Institute of Genomics and Cancer, University of Edinburgh, Crewe Road, Edinburgh, EH4 2XU, UK.
  • Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA. upeters@fredhutch.org.
  • Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA. lih@fredhutch.org.
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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