Year: 2021
Type: article
Study design: Observational Study
Abstract: Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS 1 ) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS 2 (PHS 1 , adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS 2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10 −180 ). Comparing the 80 th /20 th PHS 2 percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS 2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.
Source: Nature Communications
Authors: Minh-Phuong Huynh-Le, Chun Chieh Fan, Roshan Karunamuni, Wesley K. Thompson, Maria Elena Martinez, Rosalind A. Eeles, Zsofia Kote-Jarai, Kenneth Muir, Johanna Schleutker, Nora Pashayan, Jyotsna Batra, Henrik Grönberg, David E. Neal, Jenny L. Donovan, Freddie C. Hamdy, Richard M. Martin, Sune F. Nielsen, Børge G. Nordestgaard, Fredrik Wiklund, Catherine M. Tangen, Graham G. Giles, Alicja Wolk, Demetrius Albanes, Ruth C. Travis, William J. Blot, Wei Zheng, Maureen Sanderson, Janet L. Stanford, Lorelei A. Mucci, Catharine M. L. West, Adam S. Kibel, Olivier Cussenot, Sonja I. Berndt, Stella Koutros, Karina Dalsgaard Sørensen, Cezary Cybulski, Eli Marie Grindedal, Florence Menegaux, Kay-Tee Khaw, Jong Y. Park, Sue A. Ingles, Christiane Maier, Robert J. Hamilton, Stephen N. Thibodeau, Barry S. Rosenstein, Yong-Jie Lu, Stephen Watya, Ana Vega, Manolis Kogevinas, Kathryn L. Penney, Chad Huff, Manuel R. Teixeira, Luc Multigner, Robin J. Leach, Lisa Cannon-Albright, Hermann Brenner, Esther M. John, Radka Kaneva, Christopher J. Logothetis, Susan L. Neuhausen, Kim De Ruyck, Hardev Pandha, Azad Razack, Lisa F. Newcomb, Jay H. Fowke, Marija Gamulin, Nawaid Usmani, Frank Claessens, Manuela Gago-Dominguez, Paul A. Townsend, William S. Bush, Monique J. Roobol, Marie-Élise Parent, Jennifer J. Hu, Ian G. Mills, Ole A. Andreassen, Anders M. Dale, Tyler M. Seibert, UKGPCS collaborators, APCB (Australian Prostate Cancer BioResource), NC-LA PCaP Investigators, Canary PASS Investigators
Institutions: University of California San Diego, Moores Cancer Center, Royal Marsden NHS Foundation Trust, Institute of Cancer Research, University of Manchester, University of Warwick, University of Turku, Turku University Hospital, University of Cambridge, University College London, Translational Research Institute, Queensland University of Technology, Karolinska Institutet, Cancer Research UK, John Radcliffe Hospital, University of Oxford, Cancer Research UK Cambridge Center, Addenbrooke's Hospital, University of Bristol, NIHR Bristol Biomedical Research Centre, MRC Integrative Epidemiology Unit, University of Copenhagen, Herlev Hospital, Copenhagen University Hospital, Gentofte Hospital, Fred Hutch Cancer Center, The University of Melbourne, Cancer Council Victoria, Monash Health, Monash University, Uppsala University, Division of Cancer Epidemiology and Genetics, Vanderbilt University, International Epidemiology Institute, Vanderbilt University Medical Center, Meharry Medical College, University of Washington, Harvard University, Manchester Academic Health Science Centre, The Christie Hospital, The Christie NHS Foundation Trust, Brigham and Women's Hospital, Sorbonne Université, Assistance Publique – Hôpitaux de Paris, Hôpital Tenon, Aarhus University, Aarhus University Hospital, International Hereditary Cancer Center, Pomeranian Medical University, Oslo University Hospital, Université Paris-Sud, Inserm, Université Paris-Saclay, Centre de recherche en Epidémiologie et Santé des Populations, Moffitt Cancer Center, USC Norris Comprehensive Cancer Center, University of Toronto, Princess Margaret Cancer Centre, Mayo Clinic, Icahn School of Medicine at Mount Sinai, Queen Mary University of London, Barts Cancer Institute, Centre for Biomedical Network Research on Rare Diseases, Fundación Pública Galega de Medicina Xenómica, Instituto de Investigación Sanitaria de Santiago, Universitat Pompeu Fabra, Municipal Institute for Medical Research, Barcelona Institute for Global Health, Hospital del Mar Research Institute, The University of Texas MD Anderson Cancer Center, Universidade do Porto, IPO Porto, Instituto de Ciências Biomédicas Albel Salazar, École des Hautes Études en Santé Publique, Institut de Recherche en Santé, Environnement et Travail, Université de Rennes, The University of Texas at San Antonio Health Science Center, Mays Cancer Center at UT Health San Antonio, University of Utah, George E. Wahlen Department of VA Medical Center, German Cancer Research Center, National Center for Tumor Diseases, Deutsches Konsortium für Translationale Krebsforschung, Stanford Medicine, Stanford Cancer Institute, Stanford University, Medical University of Sofia, Beckman Research Institute, Ghent University, University of Surrey, University of Malaya, University of Tennessee Health Science Center, University Hospital Centre Zagreb, University of Zagreb, University of Alberta, Cross Cancer Institute, KU Leuven, Complejo Hospitalario Universitario de Santiago, Servicio Gallego de Salud, Health Innovation Manchester, NIHR Manchester Biomedical Research Centre, Cancer Research UK Manchester Centre, Case Western Reserve University, Erasmus MC, Institut National de la Recherche Scientifique, Université de Montréal, University of Miami, Sylvester Comprehensive Cancer Center, University of Oslo
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,560
Funders: U.S. Department of Defense, U.S. Department of Health and Human Services, U.S. Department of Veterans Affairs, University of Southern California, Vanderbilt University, University of Miami, University of Washington, Case Western Reserve University, Beckman Research Institute, City of Hope, Deutsches Krebsforschungszentrum, Sveučilište u Zagrebu, Medical University Sofia, Queen Mary University of London, Moffitt Cancer Center, Institut national de la recherche scientifique, Vanderbilt University Medical Center, NIHR Bristol Biomedical Research Centre, Instituto de Investigación Sanitaria de Santiago de Compostela, Sylvester Comprehensive Cancer Center, University of Miami Health Systems, Universitat Pompeu Fabra, University of Alberta, Cancer Research UK, National Institute for Health and Care Research, Department of Health and Social Care, University of Oxford, Institut National de la Santé et de la Recherche Médicale, University of Surrey, University of Toronto, KU Leuven, Universiteit Gent, Universiti Malaya, Universitetet i Oslo, Norges Forskningsråd, Universidade do Porto, Université Paris-Sud, Medicinski Fakultet, Sveučilište u Zagrebu, Pomorski Uniwersytet Medyczny W Szczecinie, Instituto Português de Oncologia do Porto, Deutschen Konsortium für Translationale Krebsforschung, École des Hautes Études en Santé Publique, National Institutes of Health, School of Medicine, Stanford University, Health Science Center, University of Tennessee, University of California, San Diego, School of Medicine, University of Texas Health Science Center at San Antonio, Manchester Biomedical Research Centre, Department of Internal Medicine, University of Utah, Erasmus Universitair Medisch Centrum Rotterdam, Servicio Gallego de Salud, Faculty of Medicine and Health, University of Sydney, National Cancer Institute, National Institute of Biomedical Imaging and Bioengineering, Stanford Cancer Institute
Awards: G1131969086, G128227873, G169807739, G2642749895, G2755019082, G2809956348, G298155673, G3344456887, G3433676821, G3734181317, G3765391626, G4119534169, G5271742736, G5463072094, G557084418, G5631494595, G5655537302, G5913663660, Integrating genetic testing into the prostate cancer pathway to more precisely guide care, treatment and accelerate clinical trials, G6344004923, Improving assessment of prostate cancer bone metastases using advanced diffusion imaging, G6366938697, G64423170, NIHR Senior Investigator Award, G6572568511, G6588039511, G6682065591, G6709912778, G6738454133, G675132270, G6835548964, G7491671666, G76752795, G7747255910, G7768554965, G8632625050, MRI-DERIVED CELLULARITY INDEX AS A POTENTIAL NONINVASIVE IMAGING BIOMARKER OF PROSTATE CANCER
OpenAlex ID: W3133438047