Polygenic hazard score is associated with prostate cancer in multi-ethnic populations

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 and Tyler M. Seibert ()
Additional contact information
Minh-Phuong Huynh-Le: University of California San Diego
Chun Chieh Fan: University of California San Diego
Roshan Karunamuni: University of California San Diego
Wesley K. Thompson: University of California San Diego
Maria Elena Martinez: Moores Cancer Center, Department of Family Medicine and Public Health, University of California San Diego
Rosalind A. Eeles: The Institute of Cancer Research
Zsofia Kote-Jarai: The Institute of Cancer Research
Kenneth Muir: University of Manchester, Oxford Road
Johanna Schleutker: Kiinamyllynkatu 10, FI-20014 University of Turku
Nora Pashayan: University College London, Department of Applied Health Research
Jyotsna Batra: Queensland University of Technology
Henrik Grönberg: Karolinska Institute
David E. Neal: University of Oxford, John Radcliffe Hospital
Jenny L. Donovan: Bristol Medical School, University of Bristol
Freddie C. Hamdy: University of Oxford
Richard M. Martin: Bristol Medical School, University of Bristol
Sune F. Nielsen: University of Copenhagen
Børge G. Nordestgaard: University of Copenhagen
Fredrik Wiklund: Karolinska Institute
Catherine M. Tangen: Fred Hutchinson Cancer Research Center
Graham G. Giles: Cancer Council Victoria
Alicja Wolk: Karolinska Institutet
Demetrius Albanes: National Cancer Institute, NIH
Ruth C. Travis: University of Oxford
William J. Blot: Vanderbilt University Medical Center
Wei Zheng: Vanderbilt University Medical Center
Maureen Sanderson: Meharry Medical College
Janet L. Stanford: Fred Hutchinson Cancer Research Center
Lorelei A. Mucci: Harvard T. H. Chan School of Public Health
Catharine M. L. West: University of Manchester, Manchester Academic Health Science Centre, Radiotherapy Related Research, The Christie Hospital NHS Foundation Trust
Adam S. Kibel: Brigham and Womens Hospital
Olivier Cussenot: Tenon Hospital, 4 Rue de la Chine
Sonja I. Berndt: National Cancer Institute, NIH
Stella Koutros: National Cancer Institute, NIH
Karina Dalsgaard Sørensen: Aarhus University Hospital
Cezary Cybulski: Pomeranian Medical University
Eli Marie Grindedal: Oslo University Hospital
Florence Menegaux: University Paris-Sud, University Paris-Saclay
Kay-Tee Khaw: Clinical Gerontology Unit, University of Cambridge
Jong Y. Park: Moffitt Cancer Center
Sue A. Ingles: University of Southern California/Norris Comprehensive Cancer Center
Christiane Maier: Humangenetik Tuebingen
Robert J. Hamilton: Princess Margaret Cancer Centre
Stephen N. Thibodeau: Mayo Clinic
Barry S. Rosenstein: Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place
Yong-Jie Lu: Queen Mary University of London, John Vane Science Centre, Charterhouse Square
Stephen Watya: Uro Care
Ana Vega: Fundación Pública Galega Medicina Xenómica
Manolis Kogevinas: ISGlobal
Kathryn L. Penney: Brigham and Women’s Hospital/Harvard Medical School
Chad Huff: The University of Texas M. D. Anderson Cancer Center
Manuel R. Teixeira: Portuguese Oncology Institute of Porto (IPO-Porto)
Luc Multigner: Univ Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail)—UMR_S 1085
Robin J. Leach: University of Texas Health Science Center at San Antonio
Lisa Cannon-Albright: University of Utah School of Medicine
Hermann Brenner: German Cancer Research Center (DKFZ)
Esther M. John: Stanford University School of Medicine
Radka Kaneva: Medical University of Sofia
Christopher J. Logothetis: The University of Texas M. D. Anderson Cancer Center, Department of Genitourinary Medical Oncology
Susan L. Neuhausen: Beckman Research Institute of the City of Hope
Kim De Ruyck: Ghent University, Faculty of Medicine and Health Sciences, Basic Medical Sciences
Hardev Pandha: The University of Surrey
Azad Razack: University of Malaya
Lisa F. Newcomb: Fred Hutchinson Cancer Research Center
Jay H. Fowke: Vanderbilt University Medical Center
Marija Gamulin: University Hospital Centre Zagreb, University of Zagreb, School of Medicine
Nawaid Usmani: University of Alberta
Frank Claessens: Molecular Endocrinology Laboratory, KU Leuven
Manuela Gago-Dominguez: Instituto de Investigacion Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, Servicio Galego de Saúde, SERGAS
Paul A. Townsend: Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Centre, Health Innovation Manchester, University of Manchester
William S. Bush: Cleveland Institute for Computational Biology
Monique J. Roobol: Erasmus University Medical Center
Marie-Élise Parent: Institut National de la Recherche Scientifique
Jennifer J. Hu: Sylvester Comprehensive Cancer Center
Ian G. Mills: University of Oxford
Ole A. Andreassen: Oslo University Hospital and University of Oslo
Anders M. Dale: University of California San Diego
Tyler M. Seibert: University of California San Diego

Nature Communications, 2021, vol. 12, issue 1, 1-9

Abstract: Abstract Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS2 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

Date: 2021
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DOI: 10.1038/s41467-021-21287-0

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