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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants.
Wang, Anqi; Shen, Jiayi; Rodriguez, Alex A; Saunders, Edward J; Chen, Fei; Janivara, Rohini; Darst, Burcu F; Sheng, Xin; Xu, Yili; Chou, Alisha J; Benlloch, Sara; Dadaev, Tokhir; Brook, Mark N; Plym, Anna; Sahimi, Ali; Hoffman, Thomas J; Takahashi, Atushi; Matsuda, Koichi; Momozawa, Yukihide; Fujita, Masashi; Laisk, Triin; Figuerêdo, Jéssica; Muir, Kenneth; Ito, Shuji; Liu, Xiaoxi; Uchio, Yuji; Kubo, Michiaki; Kamatani, Yoichiro; Lophatananon, Artitaya; Wan, Peggy; Andrews, Caroline; Lori, Adriana; Choudhury, Parichoy P; Schleutker, Johanna; Tammela, Teuvo L J; Sipeky, Csilla; Auvinen, Anssi; Giles, Graham G; Southey, Melissa C; MacInnis, Robert J; Cybulski, Cezary; Wokolorczyk, Dominika; Lubinski, Jan; Rentsch, Christopher T; Cho, Kelly; Mcmahon, Benjamin H; Neal, David E; Donovan, Jenny L; Hamdy, Freddie C; Martin, Richard M.
Afiliação
  • Wang A; Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Shen J; Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Rodriguez AA; Argonne National Laboratory, Lemont, IL, USA.
  • Saunders EJ; The Institute of Cancer Research, London, UK.
  • Chen F; Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Janivara R; School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA.
  • Darst BF; Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Sheng X; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
  • Xu Y; Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Chou AJ; Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Benlloch S; Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Dadaev T; Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK.
  • Brook MN; The Institute of Cancer Research, London, UK.
  • Plym A; The Institute of Cancer Research, London, UK.
  • Sahimi A; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
  • Hoffman TJ; Urology Division, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Takahashi A; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Matsuda K; Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.
  • Momozawa Y; Institute for Human Genetics, University of California, San Francisco, CA, USA.
  • Fujita M; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Laisk T; Department of Genomic Medicine, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan.
  • Figuerêdo J; Department of Computational Biology and Medical Sciences, Laboratory of Clinical Genome Sequencing, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
  • Muir K; Laboratory for Genotyping Development, RIKEN Center of Integrative Medical Sciences, Yokohama, Japan.
  • Ito S; Laboratory for Cancer Genomics, RIKEN Center of Integrative Medical Sciences, Yokohama, Japan.
  • Liu X; Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
  • Uchio Y; 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.
  • Kubo M; Warwick Medical School, University of Warwick, Coventry, UK.
  • Kamatani Y; Department of Orthopaedics, Shimane University, Izumo, Japan.
  • Lophatananon A; RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Wan P; Laboratory for Statistical and Translational Genetics, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
  • Lori A; Department of Orthopaedics, Shimane University, Izumo, Japan.
  • Choudhury PP; RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Schleutker J; Laboratory for Statistical and Translational Genetics, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
  • Tammela TLJ; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan.
  • Sipeky C; 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.
  • Auvinen A; Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Giles GG; Harvard TH Chan School of Public Health and Division of Population Sciences, Dana Farber Cancer Institute, Boston, MA, USA.
  • Southey MC; Department of Population Science, American Cancer Society, Kennesaw, GA, USA.
  • MacInnis RJ; Surveillance & Health Science Department, American Cancer Society, Kennesaw, GA, USA.
  • Cybulski C; Institute of Biomedicine, University of Turku, Turku, Finland.
  • Wokolorczyk D; Department of Medical Genetics, Genomics, Laboratory Division, Turku University Hospital, Turku, Finland.
  • Lubinski J; Department of Urology, Tampere University Hospital, Tampere, Finland.
  • Rentsch CT; Institute of Biomedicine, University of Turku, Turku, Finland.
  • Cho K; Unit of Health Sciences, Faculty of Social Sciences, Tampere University, Tampere, Finland.
  • Mcmahon BH; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
  • Neal DE; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
  • Donovan JL; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
  • Hamdy FC; Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
  • Martin RM; Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
Nat Genet ; 55(12): 2065-2074, 2023 Dec.
Article em En | MEDLINE | ID: mdl-37945903
ABSTRACT
The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Predisposição Genética para Doença Limite: Humans / Male Idioma: En Ano de publicação: 2023 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Predisposição Genética para Doença Limite: Humans / Male Idioma: En Ano de publicação: 2023 Tipo de documento: Article