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; Tyler M Seibert; 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

doi:10.1038/s41467-021-21287-0

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

Nat Commun. 2021 Feb 23;12(1):1236. doi: 10.1038/s41467-021-21287-0.

Authors

Minh-Phuong Huynh-Le^{1

2}, Chun Chieh Fan², Roshan Karunamuni^{1

2}, Wesley K Thompson^{3

4}, Maria Elena Martinez⁵, Rosalind A Eeles^{6

7}, Zsofia Kote-Jarai⁶, Kenneth Muir^{8

9}, Johanna Schleutker^{10

11}, Nora Pashayan^{12

13

14}, Jyotsna Batra^{15

16}, Henrik Grönberg¹⁷, David E Neal^{18

19

20}, Jenny L Donovan²¹, Freddie C Hamdy^{22

23}, Richard M Martin^{21

24

25}, Sune F Nielsen^{26

27}, Børge G Nordestgaard^{26

27}, Fredrik Wiklund¹⁷, Catherine M Tangen²⁸, Graham G Giles^{29

30

31}, Alicja Wolk^{32

33}, Demetrius Albanes³⁴, Ruth C Travis³⁵, William J Blot^{36

37}, Wei Zheng³⁶, Maureen Sanderson³⁸, Janet L Stanford^{39

40}, Lorelei A Mucci⁴¹, Catharine M L West⁴², Adam S Kibel⁴³, Olivier Cussenot^{44

45}, Sonja I Berndt³⁴, Stella Koutros³⁴, Karina Dalsgaard Sørensen^{46

47}, Cezary Cybulski⁴⁸, Eli Marie Grindedal⁴⁹, Florence Menegaux^{50

51}, Kay-Tee Khaw⁵², Jong Y Park⁵³, Sue A Ingles⁵⁴, Christiane Maier⁵⁵, Robert J Hamilton^{56

57}, Stephen N Thibodeau⁵⁸, Barry S Rosenstein^{59

60}, Yong-Jie Lu⁶¹, Stephen Watya⁶², Ana Vega^{63

64

65}, Manolis Kogevinas^{66

67

68}, Kathryn L Penney⁶⁹, Chad Huff⁷⁰, Manuel R Teixeira^{71

72}, Luc Multigner⁷³, Robin J Leach⁷⁴, Lisa Cannon-Albright^{75

76}, Hermann Brenner^{77

78

79}, Esther M John⁸⁰, Radka Kaneva⁸¹, Christopher J Logothetis⁸², Susan L Neuhausen⁸³, Kim De Ruyck⁸⁴, Hardev Pandha⁸⁵, Azad Razack⁸⁶, Lisa F Newcomb^{39

87}, Jay H Fowke^{88

89}, Marija Gamulin⁹⁰, Nawaid Usmani^{91

92}, Frank Claessens⁹³, Manuela Gago-Dominguez^{94

95}, Paul A Townsend⁹⁶, William S Bush⁹⁷, Monique J Roobol⁹⁸, Marie-Élise Parent^{99

100}, Jennifer J Hu¹⁰¹, Ian G Mills²², Ole A Andreassen¹⁰², Anders M Dale^{2

103}, Tyler M Seibert^{104

105

106

107}; 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 Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA.
⁵ Moores Cancer Center, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA.
⁶ The Institute of Cancer Research, London, UK.
⁷ Royal Marsden NHS Foundation Trust, London, UK.
⁸ Division of Population Health, Health Services Research and Primary Care, University of Manchester, Oxford Road, Manchester, UK.
⁹ Warwick Medical School, University of Warwick, Coventry, UK.
¹⁰ Institute of Biomedicine, Kiinamyllynkatu 10, FI-20014 University of Turku, Turku, Finland.
¹¹ Department of Medical Genetics, Genomics, Laboratory Division, Turku University Hospital, Turku, Finland.
¹² University College London, Department of Applied Health Research, London, UK.
¹³ Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Strangeways Laboratory, Worts Causeway, Cambridge, UK.
¹⁴ Department of Applied Health Research, University College London, London, UK.
¹⁵ Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
¹⁶ Translational Research Institute, Brisbane, QLD, Australia.
¹⁷ Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
¹⁸ Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Headington, Oxford, UK.
¹⁹ Department of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
²⁰ Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge, UK.
²¹ Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
²² Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
²³ Faculty of Medical Science, University of Oxford, John Radcliffe Hospital, Oxford, UK.
²⁴ National Institute for Health Research (NIHR) Biomedical Research Centre, University of Bristol, Bristol, UK.
²⁵ Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
²⁶ Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
²⁷ Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Copenhagen, Denmark.
²⁸ SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
²⁹ Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia.
³⁰ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia.
³¹ Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia.
³² Division of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
³³ Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
³⁴ Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.
³⁵ Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
³⁶ Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
³⁷ International Epidemiology Institute, Rockville, MD, USA.
³⁸ Department of Family and Community Medicine, Meharry Medical College, Nashville, TN, USA.
³⁹ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
⁴⁰ Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
⁴¹ Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
⁴² Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Radiotherapy Related Research, The Christie Hospital NHS Foundation Trust, Manchester, UK.
⁴³ Division of Urologic Surgery, Brigham and Womens Hospital, Boston, MA, USA.
⁴⁴ Sorbonne Universite, GRC n°5, AP-HP, Tenon Hospital, 4 Rue de la Chine, Paris, France.
⁴⁵ CeRePP, Tenon Hospital, Paris, France.
⁴⁶ Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
⁴⁷ Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
⁴⁸ International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
⁴⁹ Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
⁵⁰ Cancer & Environment Group, Center for Research in Epidemiology and Population Health (CESP), INSERM, University Paris-Sud, University Paris-Saclay, Villejuif Cédex, France.
⁵¹ Paris-Sud University, UMRS 1018, Villejuif Cedex, France.
⁵² Clinical Gerontology Unit, University of Cambridge, Cambridge, UK.
⁵³ Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, USA.
⁵⁴ Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
⁵⁵ Humangenetik Tuebingen, Tuebingen, Germany.
⁵⁶ Department of Surgical Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada.
⁵⁷ Department of Surgery (Urology), University of Toronto, Toronto, ON, Canada.
⁵⁸ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
⁵⁹ 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.
⁶⁰ Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁶¹ Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London, UK.
⁶² Uro Care, Kampala, Uganda.
⁶³ Fundación Pública Galega Medicina Xenómica, Santiago De Compostela, Spain.
⁶⁴ Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago De Compostela, Spain.
⁶⁵ Centro de Investigación en Red de Enfermedades Raras (CIBERER), Santiago De Compostela, Spain.
⁶⁶ ISGlobal, Barcelona, Spain.
⁶⁷ IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
⁶⁸ Universitat Pompeu Fabra (UPF), Barcelona, Spain.
⁶⁹ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, USA.
⁷⁰ The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
⁷¹ Department of Genetics, Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal.
⁷² Biomedical Sciences Institute (ICBAS), University of Porto, Porto, Portugal.
⁷³ Univ Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail)-UMR_S 1085, Rennes, France.
⁷⁴ Department of Urology, Mays Cancer Center, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
⁷⁵ Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA.
⁷⁶ George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT, USA.
⁷⁷ Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁷⁸ German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
⁷⁹ Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, Heidelberg, Germany.
⁸⁰ Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
⁸¹ Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical University of Sofia, Sofia, Bulgaria.
⁸² The University of Texas M. D. Anderson Cancer Center, Department of Genitourinary Medical Oncology, Houston, TX, USA.
⁸³ Department of Population Sciences, Beckman Research Institute of the City of Hope, Duarte, CA, USA.
⁸⁴ Ghent University, Faculty of Medicine and Health Sciences, Basic Medical Sciences, Gent, Belgium.
⁸⁵ The University of Surrey, Guildford, Surrey, UK.
⁸⁶ Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
⁸⁷ Department of Urology, University of Washington, Seattle, WA, USA.
⁸⁸ Department of Medicine and Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
⁸⁹ Division of Epidemiology, Department of Preventive Medicine, The University of Tennessee Health Science Center, Memphis, TN, USA.
⁹⁰ Department of Oncology, University Hospital Centre Zagreb, University of Zagreb, School of Medicine, Zagreb, Croatia.
⁹¹ Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada.
⁹² Division of Radiation Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada.
⁹³ Department of Cellular and Molecular Medicine, Molecular Endocrinology Laboratory, KU Leuven, Leuven, Belgium.
⁹⁴ 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.
⁹⁵ University of California San Diego, Moores Cancer Center, La Jolla, CA, USA.
⁹⁶ 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.
⁹⁷ Case Western Reserve University, Department of Population and Quantitative Health Sciences, Cleveland Institute for Computational Biology, Cleveland, OH, USA.
⁹⁸ Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁹⁹ Epidemiology and Biostatistics Unit, Centre Armand-Frappier Santé Biotechnologie, Institut National de la Recherche Scientifique, Laval, QC, Canada.
¹⁰⁰ Department of Social and Preventive Medicine, School of Public Health, University of Montreal, Montreal, QC, Canada.
¹⁰¹ The University of Miami School of Medicine, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
¹⁰² NORMENT, KG Jebsen Centre, Oslo University Hospital and University of Oslo, Oslo, Norway.
¹⁰³ Department of Radiology, University of California San Diego, La Jolla, CA, USA.
¹⁰⁴ Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA. tseibert@ucsd.edu.
¹⁰⁵ Center for Multimodal Imaging and Genetics, University of California San Diego, La Jolla, CA, USA. tseibert@ucsd.edu.
¹⁰⁶ Department of Radiology, University of California San Diego, La Jolla, CA, USA. tseibert@ucsd.edu.
¹⁰⁷ Department of Bioengineering, University of California San Diego, La Jolla, CA, USA. tseibert@ucsd.edu.

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 < 10^-180). Comparing the 80^th/20^th 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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Aged
Ethnicity / genetics*
Humans
Male
Middle Aged
Multifactorial Inheritance / genetics*
Multivariate Analysis
Neoplasm Invasiveness
Prostatic Neoplasms / genetics*
Self Report

Abstract

Publication types

MeSH terms

Grants and funding