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

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  • Minh-Phuong Huynh-Le, Department of Dermatology, University of California, San Diego, California; Department of Pediatrics, University of California, San Diego, California; Rady Children's Hospital, San Diego, California.
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  • Chun Chieh Fan, Department of Dermatology, University of California, San Diego, California; Department of Pediatrics, University of California, San Diego, California; Rady Children's Hospital, San Diego, California.
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  • Roshan Karunamuni, Department of Dermatology, University of California, San Diego, California; Department of Pediatrics, University of California, San Diego, California; Rady Children's Hospital, San Diego, California.
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  • Wesley K Thompson, Department of Dermatology, University of California, San Diego, California; Department of Pediatrics, University of California, San Diego, California; Rady Children's Hospital, San Diego, California.
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  • Maria Elena Martinez, Department of Dermatology, University of California, San Diego, California; Department of Pediatrics, University of California, San Diego, California; Rady Children's Hospital, San Diego, California.
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  • Rosalind A Eeles, The Royal Marsden / The Institute of Cancer Research National Institute for Health Research Biomedical Research Centre, London, UK.
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  • Zsofia Kote-Jarai, The Royal Marsden / The Institute of Cancer Research National Institute for Health Research Biomedical Research Centre, London, UK.
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  • Kenneth Muir, Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK Manchester Centre for Genomic Medicine, University of Manchester, Manchester, UK.
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  • Johanna Schleutker, Turku PET Centre and Division of Clinical Neurosciences Turku, University of Turku and Turku University Hospital, Turku, Finland.
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  • Nora Pashayan, London Ctr Nanotechnol, University College London, University of London
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  • Jyotsna Batra, Queensland University of Technology
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  • Henrik Grönberg, Karolinska University Hospital og Karolinska Institute
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  • David E Neal, Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, United Kingdom; Department of Physics, University of Oxford, Oxford, United Kingdom; University of Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
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  • Jenny L Donovan, MRC Integrative Epidemiology Unit, University of Bristol, Bristol, England2School of Social and Community Medicine, University of Bristol, Bristol, England.
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  • Freddie C Hamdy, Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, United Kingdom; Department of Physics, University of Oxford, Oxford, United Kingdom; University of Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
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  • Richard M Martin, MRC Integrative Epidemiology Unit, University of Bristol, Bristol, England2School of Social and Community Medicine, University of Bristol, Bristol, England.
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  • Sune F Nielsen, Københavns Universitet - Graduate School of Health and Medical Sciences Faculty of Health and Medical Sciences
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  • Børge G Nordestgaard, 1Copenhagen University Hospital, Copenhagen, Denmark. 2Aarhus University Hospital, Aarhus, Denmark. 3University of Copenhagen, Copenhagen, Denmark. 4Odense University Hospital, Odense, Denmark.
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  • Fredrik Wiklund, Karolinska University Hospital og Karolinska Institute
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  • Catherine M Tangen, SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington.
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  • Graham G Giles, Division of Cancer Epidemiology and Prevention, Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland; Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
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  • Alicja Wolk, Karolinska Univ Hosp, Karolinska University Hospital, Karolinska Institutet, Dept Neurosurg
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  • Demetrius Albanes, National Institute of Health's National Cancer Institute: Quantitative Imaging Network
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  • Ruth C Travis, Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, United Kingdom; Department of Physics, University of Oxford, Oxford, United Kingdom; University of Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
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  • William J Blot, Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.
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  • Wei Zheng, Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.
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  • Maureen Sanderson, Meharry Medical College
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  • Janet L Stanford, Fred Hutchinson Cancer Research Center
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  • Lorelei A Mucci, Harvard TH Chan Sch Publ Hlth, Harvard T.H. Chan School of Public Health
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  • Catharine M L West, Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK Manchester Centre for Genomic Medicine, University of Manchester, Manchester, UK.
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  • Adam S Kibel, Brigham and Womens Hospital, Harvard Medical School, Boston, MA, USA
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  • Olivier Cussenot, Tenon Hospital
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  • Sonja I Berndt, National Institute of Health's National Cancer Institute: Quantitative Imaging Network
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  • Stella Koutros, National Institute of Health's National Cancer Institute: Quantitative Imaging Network
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  • Karina Dalsgaard Sørensen
  • Cezary Cybulski, Pomeranian Med Univ, Pomeranian Medical University
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  • Eli Marie Grindedal, Department of Gynaecologic Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. Institute for Cancer Genetics and Informatics, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. Faculty of Medicine, University of Oslo, Oslo, Norway.
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  • Florence Menegaux, Univ Paris 11, University of Paris Sud - Paris XI, Lab Geosci Paris Sud GEOPS, UMR 8148
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  • Kay-Tee Khaw, Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom; Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom;
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  • Jong Y Park, Moffitt Cancer Center
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  • Sue A Ingles, University of Southern California/Norris Comprehensive Cancer Center
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  • Christiane Maier, Humangenetik Tuebingen
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  • Robert J Hamilton, Toronto Western Hosp, University of Toronto, University Health Network Toronto
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  • Stephen N Thibodeau, Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, NY
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  • Barry S Rosenstein, Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of
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  • Yong-Jie Lu, Queen Mary Univ London, Queen Mary University London, University of London, Barts & London Sch Med & Denistry
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  • Stephen Watya, Uro Care
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  • Ana Vega, Fundación Pública Galega de Medicina Xenómica-SERGAS
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  • Manolis Kogevinas, ISGlobal, ISGlobal
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  • Kathryn L Penney, Harvard Medical School / Brigham and Women's Hospital
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  • UKGPCS collaborators

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 < 10-180). Comparing the 80th/20th PHS2 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. PHS2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.

Original languageEnglish
Article number1236
JournalNature Communications
Volume12
Issue1
Number of pages9
ISSN2041-1723
DOIs
Publication statusPublished - Feb 2021

    Research areas

  • Aged, Ethnic Groups/genetics, Humans, Male, Middle Aged, Multifactorial Inheritance/genetics, Multivariate Analysis, Neoplasm Invasiveness, Prostatic Neoplasms/genetics, Self Report

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