Title

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction

Authors

David V. Conti, Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Burcu F. Darst, Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Lilit C. Moss, Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Edward J. Saunders, The Institute of Cancer Research, London, UK.
Xin Sheng, Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Alisha Chou, Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Fredrick R. Schumacher, Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA.
Ali Amin Olama, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
Sara Benlloch, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
Tokhir Dadaev, The Institute of Cancer Research, London, UK.
Mark N. Brook, The Institute of Cancer Research, London, UK.
Ali Sahimi, Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Thomas J. Hoffmann, Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.
Atushi Takahashi, Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Koichi Matsuda, Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
Yukihide Momozawa, Laboratory for Genotyping Development, RIKEN Center of Integrative Medical Sciences, Yokohama, Japan.
Masashi Fujita, Laboratory for Cancer Genomics, RIKEN Center of Integrative Medical Sciences, Yokohama, Japan.
Kenneth Muir, Division of Population Health, Health Services Research and Primary Care, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Artitaya Lophatananon, Division of Population Health, Health Services Research and Primary Care, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Peggy Wan, Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Loic Le Marchand, Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
Lynne R. Wilkens, Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
Victoria L. Stevens, Behavioral and Epidemiology Research Group, Research Program, American Cancer Society, Atlanta, GA, USA.
Susan M. Gapstur, Behavioral and Epidemiology Research Group, Research Program, American Cancer Society, Atlanta, GA, USA.
Brian D. Carter, Behavioral and Epidemiology Research Group, Research Program, American Cancer Society, Atlanta, GA, USA.
Johanna Schleutker, Institute of Biomedicine, University of Turku, Turku, Finland.
Teuvo L. Tammela, Department of Urology, Tampere University Hospital and Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Csilla Sipeky, Institute of Biomedicine, University of Turku, Turku, Finland.
Anssi Auvinen, Unit of Health Sciences, Faculty of Social Sciences, Tampere University, Tampere, Finland.
Graham G. Giles, Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
Melissa C. Southey, Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
Robert J. MacInnis, Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
Cezary Cybulski, International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.

Document Type

Article

Publication Date

1-1-2021

Abstract

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.

Publication Source (Journal or Book title)

Nature genetics

First Page

65

Last Page

75

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