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

Huynh-Le MP 1 , Fan CC 2 , Karunamuni R 1 , Thompson WK 3 , Martinez ME 4 , Eeles RA 5 Show all authors , Kote-Jarai Z 5 , Muir K 6 , Schleutker J 7 , Pashayan N 8 , Batra J 9 , Grönberg H 10 , Neal DE 11 , Donovan JL 12 , Hamdy FC 13 , Martin RM 12 , Nielsen SF 14 , Nordestgaard BG 14 , Wiklund F 10 , Tangen CM 15 , Giles GG 16 , Wolk A 17 , Albanes D 18 , Travis RC 19 , Blot WJ 20 , Zheng W 20 , Sanderson M 21 , Stanford JL 22 , Mucci LA 23 , West CML 24 , Kibel AS 25 , Cussenot O 26 , Berndt SI 18 , Koutros S 18 , Sørensen KD 27 , Cybulski C 28 , Grindedal EM 29 , Menegaux F 30 , Khaw KT 31 , Park JY 32 , Ingles SA 33 , Maier C 34 , Hamilton RJ 35 , Thibodeau SN 36 , Rosenstein BS 37 , Lu YJ 38 , Watya S 39 , Vega A 40 , Kogevinas M 41 , Penney KL 42 , Huff C 43 , Teixeira MR 44 , Multigner L 45 , Leach RJ 46 , Cannon-Albright L 47 , Brenner H 48 , John EM 49 , Kaneva R 50 , Logothetis CJ 51 , Neuhausen SL 52 , De Ruyck K 53 , Pandha H 54 , Razack A 55 , Newcomb LF 22 , Fowke JH 56 , Gamulin M 57 , Usmani N 58 , Claessens F 59 , Gago-Dominguez M 60 , Townsend PA 61 , Bush WS 62 , Roobol MJ 63 , Parent MÉ 64 , Hu JJ 65 , Mills IG 13 , Andreassen OA 66 , Dale AM 2 , Seibert TM 67 , UKGPCS collaborators , APCB (Australian Prostate Cancer BioResource) , NC-LA PCaP Investigators , IMPACT Study Steering Committee and Collaborators , Canary PASS Investigators , Profile Study Steering Committee , PRACTICAL Consortium

Affiliations 

  • 1 Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA
  • 2 Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA, USA
  • 3 Division of Biostatistics and Halicioğlu Data Science Institute, University of California San Diego, La Jolla, CA, USA
  • 4 Moores Cancer Center, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA
  • 5 The Institute of Cancer Research, London, UK
  • 6 Division of Population Health, Health Services Research and Primary Care, University of Manchester, Oxford Road, Manchester, UK
  • 7 Institute of Biomedicine, Kiinamyllynkatu 10, FI-20014 University of Turku, Turku, Finland
  • 8 University College London, Department of Applied Health Research, London, UK
  • 9 Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia
  • 10 Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
  • 11 Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Headington, Oxford, UK
  • 12 Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
  • 13 Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
  • 14 Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  • 15 SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  • 16 Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia
  • 17 Division of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
  • 18 Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA
  • 19 Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
  • 20 Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
  • 21 Department of Family and Community Medicine, Meharry Medical College, Nashville, TN, USA
  • 22 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  • 23 Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA
  • 24 Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Radiotherapy Related Research, The Christie Hospital NHS Foundation Trust, Manchester, UK
  • 25 Division of Urologic Surgery, Brigham and Womens Hospital, Boston, MA, USA
  • 26 Sorbonne Universite, GRC n°5, AP-HP, Tenon Hospital, 4 Rue de la Chine, Paris, France
  • 27 Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
  • 28 International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
  • 29 Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
  • 30 Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif Cédex, France
  • 31 Clinical Gerontology Unit, University of Cambridge, Cambridge, UK
  • 32 Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA
  • 33 Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA
  • 34 Humangenetik Tuebingen, Tuebingen, Germany
  • 35 Department of Surgical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada
  • 36 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
  • 37 Department of Radiation Oncology and Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, USA
  • 38 Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London, UK
  • 39 Uro Care, Kampala, Uganda
  • 40 Fundación Pública Galega Medicina Xenómica, Santiago De Compostela, Spain
  • 41 ISGlobal, Barcelona, Spain
  • 42 Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA
  • 43 The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA
  • 44 Department of Genetics, Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal
  • 45 Univ Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail)-UMR_S 1085, Rennes, France
  • 46 Department of Urology, Mays Cancer Center, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
  • 47 Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA
  • 48 Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 49 Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA
  • 50 Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical University of Sofia, Sofia, Bulgaria
  • 51 The University of Texas M. D. Anderson Cancer Center, Department of Genitourinary Medical Oncology, Houston, TX, USA
  • 52 Department of Population Sciences, Beckman Research Institute of the City of Hope, Duarte, CA, USA
  • 53 Ghent University, Faculty of Medicine and Health Sciences, Basic Medical Sciences, Gent, Belgium
  • 54 The University of Surrey, Guildford, Surrey, UK
  • 55 Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 56 Department of Medicine and Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
  • 57 Department of Oncology, University Hospital Centre Zagreb, University of Zagreb, School of Medicine, Zagreb, Croatia
  • 58 Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada
  • 59 Department of Cellular and Molecular Medicine, Molecular Endocrinology Laboratory, KU Leuven, Leuven, Belgium
  • 60 Genomic Medicine Group, Galician Foundation of Genomic Medicine, Instituto de Investigacion Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago, Servicio Galego de Saúde, SERGAS, Santiago de Compostela, Spain
  • 61 Division of Cancer Sciences, Manchester Cancer Research Centre, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Centre, Health Innovation Manchester, University of Manchester, Manchester, UK
  • 62 Case Western Reserve University, Department of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Cleveland, OH, USA
  • 63 Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands
  • 64 Epidemiology and Biostatistics Unit, Centre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique, Laval, QC, Canada
  • 65 The University of Miami School of Medicine, Sylvester Comprehensive Cancer Center, Miami, FL, USA
  • 66 NORMENT, KG Jebsen Centre, Oslo University Hospital and University of Oslo, Oslo, Norway
  • 67 Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA. tseibert@ucsd.edu
Nat Commun, 2021 02 23;12(1):1236.
PMID: 33623038 DOI: 10.1038/s41467-021-21287-0

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 

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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