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  • Clinical Research
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Additional SNPs improve risk stratification of a polygenic hazard score for prostate cancer

Prostate Cancer and Prostatic Diseases volume 24, pages 532–541 (2021)Cite this article

Subjects

Abstract

Background

Polygenic hazard scores (PHS) can identify individuals with increased risk of prostate cancer. We estimated the benefit of additional SNPs on performance of a previously validated PHS (PHS46).

Materials and method

180 SNPs, shown to be previously associated with prostate cancer, were used to develop a PHS model in men with European ancestry. A machine-learning approach, LASSO-regularized Cox regression, was used to select SNPs and to estimate their coefficients in the training set (75,596 men). Performance of the resulting model was evaluated in the testing/validation set (6,411 men) with two metrics: (1) hazard ratios (HRs) and (2) positive predictive value (PPV) of prostate-specific antigen (PSA) testing. HRs were estimated between individuals with PHS in the top 5% to those in the middle 40% (HR95/50), top 20% to bottom 20% (HR80/20), and bottom 20% to middle 40% (HR20/50). PPV was calculated for the top 20% (PPV80) and top 5% (PPV95) of PHS as the fraction of individuals with elevated PSA that were diagnosed with clinically significant prostate cancer on biopsy.

Results

166 SNPs had non-zero coefficients in the Cox model (PHS166). All HR metrics showed significant improvements for PHS166 compared to PHS46: HR95/50 increased from 3.72 to 5.09, HR80/20 increased from 6.12 to 9.45, and HR20/50 decreased from 0.41 to 0.34. By contrast, no significant differences were observed in PPV of PSA testing for clinically significant prostate cancer.

Conclusions

Incorporating 120 additional SNPs (PHS166 vs PHS46) significantly improved HRs for prostate cancer, while PPV of PSA testing remained the same.

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Fig. 1: Cumulative incidence curves for PHS166.

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Data availability

The data used in this work were obtained from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. Readers who are interested in accessing the data must first submit a proposal to the Data Access Committee. If the reader is not a member of the consortium, their concept form must be sponsored by a principal investigator (PI) of one of the PRACTICAL consortium member studies. If approved by the Data Access Committee, PIs within the consortium, each of whom retains ownership of their data submitted to the consortium, can then choose to participate in the specific proposal. In addition, portions of the data are available for request from dbGaP (database of Genotypes and Phenotypes) which is maintained by the National Center for Biotechnology Information (NCBI): https://www.ncbi.nlm.nih.gov/gap/?term=Icogs+prostatehttps://www.ncbi.nlm.nih.gov/gap/?term=Icogs+prostate. Anyone can apply to join the consortium. The eligibility requirements are listed here: http://practical.icr.ac.uk/blog/?page_id=9. Joining the consortium would not guarantee access, as a proposal for access would still be submitted to the Data Access Committee, but there would be no need for a separate member sponsor. Readers may find information about application by using the contact information below: Rosalind Eeles Principal Investigator for PRACTICAL Professor of Oncogenetics Institute of Cancer Research (ICR) Sutton, UK Email: PRACTICAL@icr.ac.uk URL: http://practical.icr.ac.uk Tel: ++44 (0)20 8722 4094.

References

  1. Seibert TM, Fan CC, Wang Y, Zuber V, Karunamuni R, Parsons JK, et al. Polygenic hazard score to guide screening for aggressive prostate cancer: Development and validation in large scale cohorts. BMJ. 2018;360:1–7.

    Google Scholar 

  2. Huynh-Le MP, Myklebust TÅ, Feng CH, Karunamuni R, Johannesen TB, Dale AM, et al. Age dependence of modern clinical risk groups for localized prostate cancer—a population-based study. Cancer. 2020;126:1691–9.

    Article  Google Scholar 

  3. Pashayan N, Duffy SW, Chowdhury S, Dent T, Burton H, Neal DE, et al. Polygenic susceptibility to prostate and breast cancer: Implications for personalised screening. Br J Cancer. 2011;104:1656–63.

    Article  CAS  Google Scholar 

  4. Witte JS. Personalized prostate cancer screening: improving PSA tests with genomic information. Sci Transl Med. 2010;2:1–5.

    Article  Google Scholar 

  5. Chen H, Liu X, Brendler CB, Ankerst DP, Leach RJ, Goodman PJ, et al. Adding genetic risk score to family history identifies twice as many high-risk men for prostate cancer: Results from the prostate cancer prevention trial. Prostate. 2016;76:1120–9.

    Article  Google Scholar 

  6. Huynh-Le M-P, Fan CC, Karunamuni R, Thompson WK, Martinez ME, Eeles RA, et al. Polygenic hazard score is associated with prostate cancer in multi-ethnic populations. medRxiv. 2020:1–34.

  7. Schumacher FR, Al Olama AA, Berndt SI, Benlloch S, Ahmed M, Saunders EJ, et al. Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci. Nat Genet. 2018;50:928–36.

    Article  CAS  Google Scholar 

  8. Kote-Jarai Z, Easton DF, Stanford JL, Ostrander EA, Schleutker J, Ingles SA, et al. Multiple novel prostate cancer predisposition loci confirmed by an international study: The PRACTICAL consortium. Cancer Epidemiol Biomark Prev. 2008;17:2052–61.

    Article  CAS  Google Scholar 

  9. Eeles RA, Olama AAAl, Benlloch S, Saunders EJ, Leongamornlert DA, Tymrakiewicz M, et al. Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. Nat Genet. 2013;45:385–91.

    Article  CAS  Google Scholar 

  10. Tibshiranit BR. Regression shrinkage and selection via the Lasso. J R Stat Soc B. 1996:267–88.

  11. Tibshirani R. The lasso method for variable selection in the cox model. Stat Med. 1997;16:385–95.

    Article  CAS  Google Scholar 

  12. Mavaddat N, Michailidou K, Dennis J, Lush M, Fachal L, Lee A, et al. Polygenic risk scores for prediction of breast cancer and breast cancer subtypes. Am J Hum Genet. 2019;104:21–34.

    Article  CAS  Google Scholar 

  13. Amos CI, Dennis J, Wang Z, Byun J, Schumacher FR, Gayther SA, et al. The oncoarray consortium: a network for understanding the genetic architecture of common cancers. Cancer Epidemiol Biomark Prev. 2017;26:126–35.

    Article  Google Scholar 

  14. Eeles R. Prostate cancer genome-wide association study from 89,000 men using the OncoArray chip to identify novel prostate cancer susceptibility loci. J Clin Oncol. 2016;34:1525.

    Article  Google Scholar 

  15. Karunamuni RA, Huynh-Le MP, Fan CC, Eeles RA, Easton DF, Kote-Jarai ZsS, et al. The effect of sample size on polygenic hazard models for prostate cancer. Eur J Hum Genet. 2020. https://doi.org/10.1038/s41431-020-0664-2.

  16. Li Y, Byun J, Cai G, Xiao X, Han Y, Cornelis O, et al. FastPop: a rapid principal component derived method to infer intercontinental ancestry using genetic data. BMC Bioinforma. 2016;17:1–8.

    Article  Google Scholar 

  17. Heller G. A measure of explained risk in the proportional hazards model. Biostatistics. 2012;13:315–25.

    Article  Google Scholar 

  18. NCCN Clinical Practice Guidelines in Oncology. Prostate Cancer. Version 1.2019.

  19. Therneau TM, Li H. Computing the Cox model for case cohort designs. Lifetime Data Anal. 1999;5:99–112.

    Article  CAS  Google Scholar 

  20. Huynh-Le M-P, Fan CC, Karunamuni R, Walsh EI, Turner EL, Lane JA, et al. A genetic risk score to personalize prostate cancer screening, applied to population data. Cancer Epidemiol Biomarkers Prev. 2020;29:1731–8.

    Article  Google Scholar 

  21. Prostate Cancer Incidence Statistics Cancer Research UK. https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/prostate-cancer/incidence#heading-one. Accessed 23 Jul 2020.

  22. Martin RM, Donovan JL, Turner EL, Metcalfe C, Young GJ, Walsh EI, et al. Effect of a low-intensity PSA-based screening intervention on prostate cancer mortality: the CAP randomized clinical trial. J Am Med Assoc. 2018;319:883–95.

    Article  Google Scholar 

  23. Landrum MJ, Lee JM, Riley GR, Jang W, Rubinstein WS, Church DM, et al. ClinVar: Public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res. 2014;42:980–85.

    Article  Google Scholar 

  24. Torkamani A, Wineinger NE, Topol EJ. The personal and clinical utility of polygenic risk scores. Nat Rev Genet. 2018;19:581–90.

    Article  CAS  Google Scholar 

  25. Pashayan N, Duffy SW, Neal DE, Hamdy FC, Donovan JL, Martin RM, et al. Implications of polygenic risk-stratified screening for prostate cancer on overdiagnosis. Genet Med. 2015;17:789–95.

    Article  Google Scholar 

  26. Pashayan N, Pharoah PDP, Schleutker J, Talala K, Tammela TLJ, Määttänen L, et al. Reducing overdiagnosis by polygenic risk-stratified screening: findings from the Finnish section of the ERSPC. Br J Cancer. 2015;113:1086–93.

    Article  CAS  Google Scholar 

  27. Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Omland T, et al. Plasma natriuretic peptide levels and the risk of cardiovascular events and death. N Engl J Med. 2004;350:655–63.

    Article  CAS  Google Scholar 

  28. Yang X, Leslie G, Gentry-Maharaj A, Ryan A, Intermaggio M, Lee A, et al. Evaluation of polygenic risk scores for ovarian cancer risk prediction in a prospective cohort study. J Med Genet. 2018;55:546–54.

    Article  CAS  Google Scholar 

  29. Yeh HC, Duncan BB, Schmidt MI, Wang NY, Brancati FL. Smoking, smoking cessation, and risk for type 2 diabetes mellitus: a cohort study. Ann Intern Med. 2010;152:10–7.

    Article  Google Scholar 

  30. Ren S, Xu J, Zhou T, Jiang H, Chen H, Liu F, et al. Plateau effect of prostate cancer risk-associated SNPs in discriminating prostate biopsy outcomes. Prostate. 2013;73:1824–35.

    Article  CAS  Google Scholar 

  31. Forgetta V, Keller-baruch J, Forest M, Durand A, Bhatnagar S, Kemp JP, et al. Development of a polygenic risk score to improve screening for fracture risk: a genetic risk prediction study. PLoS Med. 2020;17:1–19.

    Article  Google Scholar 

  32. Chen T-H, Chatterjee N, Landi MT, Shi J. A penalized regression framework for building polygenic risk models based on summary statistics from genome-wide association studies and incorporating external information. J Am Stat Assoc. 2020;1459:1–19.

    Google Scholar 

  33. Karunamuni R, Huynh-Le M-P, Fan CC, Thompson W, Eeles RA, Kote-Jarai Z, et al. African-specific improvement of a polygenic hazard score for age at diagnosis of prostate cancer. International Journal of Cancer. 2021;148:99–105.

    Article  CAS  Google Scholar 

  34. McNeish DM. Using Lasso for predictor selection and to assuage overfitting: a method long overlooked in behavioral sciences. Multivar Behav Res. 2015;50:471–84.

    Article  Google Scholar 

Download references

Funding

This study was funded in part by a grant from the United States National Institute of Health/National Institute of Biomedical Imaging and Bioengineering (#K08EB026503), the University of California Cancer Research Coordinating Committee (#C21CR2060), the Research Council of Norway (#223273), KG Jebsen Stiftelsen, and South East Norway Health Authority.

Author information

Author notes

  1. Additional consortia members, associated funding, and contact information are provided in the Supplementary Data Appendix 1, 2, and 3.

Authors and Affiliations

  1. Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA

    Roshan A. Karunamuni & Tyler M. Seibert

  2. Radiation Oncology, George Washington University, Washington, DC, USA

    Minh-Phuong Huynh-Le

  3. Center for Human Development, University of California San Diego, La Jolla, CA, USA

    Chun C. Fan

  4. Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA, USA

    Wesley Thompson

  5. The Institute of Cancer Research, London, SM2 5NG, UK

    Rosalind A. Eeles & Zsofia Kote-Jarai

  6. Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK

    Rosalind A. Eeles

  7. Division of Population Health, Health Services Research and Primary Care, University of Manchester, Oxford Road, Manchester, M13 9PL, UK

    Kenneth Muir & Artitaya Lophatananon

  8. Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK

    Kenneth Muir

  9. Institute of Biomedicine, University of Turku, Turku, Finland

    Johanna Schleutker

  10. Department of Medical Genetics, Genomics, Laboratory Division, Turku University Hospital, PO Box 52, 20521, Turku, Finland

    Johanna Schleutker

  11. Department of Applied Health Research, University College London, London, WC1E 7HB, UK

    Nora Pashayan

  12. Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Strangeways Laboratory, Worts Causeway, Cambridge, CB1 8RN, UK

    Nora Pashayan

  13. Australian Prostate Cancer Research Centre-Qld, Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, 4059, Australia

    Jyotsna Batra

  14. Translational Research Institute, Brisbane, QLD, 4102, Australia

    Jyotsna Batra

  15. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, SE-171 77, Stockholm, Sweden

    Henrik Grönberg & Fredrik Wiklund

  16. Bristol Medical School, Department of Population Health Sciences, University of Bristol, Bristol, UK

    Eleanor I. Walsh, Emma L. Turner, Athene Lane & Richard M. Martin

  17. MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK

    Athene Lane & Richard M. Martin

  18. National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, UK

    Richard M. Martin

  19. Nuffield Department of Surgical Sciences, University of Oxford, Room 6603, Level 6, John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU, UK

    David E. Neal & Freddie C. Hamdy

  20. Department of Oncology, University of Cambridge, Box 279, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 0QQ, UK

    David E. Neal

  21. Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge, CB2 0RE, UK

    David E. Neal

  22. School of Social and Community Medicine, University of Bristol, Bristol, UK

    Jenny L. Donovan

  23. Faculty of Medical Science, University of Oxford, John Radcliffe Hospital, Oxford, UK

    Freddie C. Hamdy

  24. Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark

    Børge G. Nordestgaard & Sune F. Nielsen

  25. Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, 2200, Copenhagen, Denmark

    Børge G. Nordestgaard

  26. SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Catherine M. Tangen

  27. Cancer Epidemiology Division, Cancer Council Victoria, 615 St Kilda Road, Melbourne, VIC, 3004, Australia

    Robert J. MacInnis

  28. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Grattan Street, Parkville, VIC, 3010, Australia

    Robert J. MacInnis

  29. Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, SE-171 77, Stockholm, Sweden

    Alicja Wolk

  30. Department of Surgical Sciences, Uppsala University, 75185, Uppsala, Sweden

    Alicja Wolk

  31. Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, 20892, USA

    Demetrius Albanes, Sonja I. Berndt & Stella Koutros

  32. Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, 90015, USA

    Christopher A. Haiman

  33. Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK

    Ruth C. Travis

  34. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109-1024, USA

    Janet L. Stanford & Lisa F. Newcomb

  35. Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, 98195, USA

    Janet L. Stanford

  36. Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, 02115, USA

    Lorelei A. Mucci

  37. Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Radiotherapy Related Research, The Christie Hospital NHS Foundation Trust, Manchester, M13 9PL, UK

    Catharine M. L. West

  38. Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, 2200, Copenhagen, Denmark

    Sune F. Nielsen

  39. Division of Urologic Surgery, Brigham and Womens Hospital, 75 Francis Street, Boston, MA, 02115, USA

    Adam S. Kibel

  40. Sorbonne Universite, GRC n°5, AP-HP, Tenon Hospital, 4 rue de la Chine, F-75020, Paris, France

    Olivier Cussenot

  41. CeRePP, Tenon Hospital, F-75020, Paris, France

    Olivier Cussenot

  42. Department of Molecular Medicine, Aarhus University Hospital, Palle Juul-Jensen Boulevard 99, 8200, Aarhus, Denmark

    Karina Dalsgaard Sørensen

  43. Department of Clinical Medicine, Aarhus University, DK-8200, Aarhus, Denmark

    Karina Dalsgaard Sørensen

  44. International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, 70-115, Szczecin, Poland

    Cezary Cybulski

  45. Department of Medical Genetics, Oslo University Hospital, 0424, Oslo, Norway

    Eli Marie Grindedal

  46. Department of Cancer Epidemiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL, 33612, USA

    Jong Y. Park

  47. Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, 90015, USA

    Sue A. Ingles

  48. Humangenetik Tuebingen, Paul-Ehrlich-Str 23, D-72076, Tuebingen, Germany

    Christiane Maier

  49. Dept. of Surgical Oncology, Princess Margaret Cancer Centre, Toronto, ON, M5G 2M9, Canada

    Robert J. Hamilton

  50. Dept. of Surgery (Urology), University of Toronto, Toronto, ON, Canada

    Robert J. Hamilton

  51. Department of Radiation Oncology and Department of Genetics and Genomic Sciences, Box 1236, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA

    Barry S. Rosenstein

  52. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029-5674, USA

    Barry S. Rosenstein

  53. Fundación Pública Galega Medicina Xenómica, Santiago de Compostela, 15706, Spain

    Ana Vega

  54. Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago De Compostela, 15706, Spain

    Ana Vega

  55. Centro de Investigación en Red de Enfermedades Raras (CIBERER), Santiago De Compostela, Spain

    Ana Vega

  56. ISGlobal, Barcelona, Spain

    Manolis Kogevinas

  57. IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain

    Manolis Kogevinas

  58. Universitat Pompeu Fabra (UPF), Barcelona, Spain

    Manolis Kogevinas

  59. CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain

    Manolis Kogevinas

  60. Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital/Harvard Medical School, Boston, MA, 02184, USA

    Kathryn L. Penney

  61. Department of Genetics, Portuguese Oncology Institute of Porto (IPO-Porto), 4200-072, Porto, Portugal

    Manuel R. Teixeira

  62. Biomedical Sciences Institute (ICBAS), University of Porto, 4050-313, Porto, Portugal

    Manuel R. Teixeira

  63. Cancer Genetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), 4200-072, Porto, Portugal

    Manuel R. Teixeira

  64. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), D-69120, Heidelberg, Germany

    Hermann Brenner

  65. German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), D-69120, Heidelberg, Germany

    Hermann Brenner

  66. Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, 69120, Heidelberg, Germany

    Hermann Brenner

  67. Departments of Epidemiology & Population Health and of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, 94304, USA

    Esther M. John

  68. Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical University of Sofia, Sofia, 2 Zdrave Str., 1431, Sofia, Bulgaria

    Radka Kaneva

  69. The University of Texas M. D. Anderson Cancer Center, Department of Genitourinary Medical Oncology, 1515 Holcombe Blvd., Houston, TX, 77030, USA

    Christopher J. Logothetis

  70. Department of Population Sciences, Beckman Research Institute of the City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA

    Susan L. Neuhausen

  71. Department of Surgery, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Azad Razack

  72. Department of Urology, University of Washington, 1959 NE Pacific Street, Box 356510, Seattle, WA, 98195, USA

    Lisa F. Newcomb

  73. Division of Medical Oncology, Urogenital Unit, Department of Oncology, University Hospital Centre Zagreb, University of Zagreb, School of Medicine, 10000, Zagreb, Croatia

    Marija Gamulin

  74. Department of Oncology, Cross Cancer Institute, University of Alberta, 11560 University Avenue, Edmonton, AB, T6G 1Z2, Canada

    Nawaid Usmani

  75. Division of Radiation Oncology, Cross Cancer Institute, 11560 University Avenue, Edmonton, AB, T6G 1Z2, Canada

    Nawaid Usmani

  76. Molecular Endocrinology Laboratory, Department of Cellular and Molecular Medicine, KU, Leuven, BE-3000, Belgium

    Frank Claessens

  77. 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, 15706, Santiago de Compostela, Spain

    Manuela Gago-Dominguez

  78. University of California San Diego, Moores Cancer Center, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, 92093-0012, USA

    Manuela Gago-Dominguez

  79. 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, Univeristy of Manchester, M13 9WL, Manchester, UK

    Paul A. Townsend

  80. Department of Urology, Erasmus University Medical Center, 3015 CE, Rotterdam, The Netherlands

    Monique J. Roobol

  81. Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, 2525 West End Avenue, Suite 800, Nashville, TN, 37232, USA

    Wei Zheng

  82. Center for Cancer Research and Cell Biology, Queen’s University of Belfast, Belfast, UK

    Ian G. Mills

  83. NORMENT, KG Jebsen Centre, Oslo University Hospital and University of Oslo, Oslo, Norway

    Ole A. Andreassen

  84. Department of Radiology, University of California San Diego, La Jolla, CA, USA

    Anders M. Dale & Tyler M. Seibert

  85. Department of Bioengineering, University of California San Diego, La Jolla, CA, USA

    Tyler M. Seibert

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  1. Roshan A. Karunamuni
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  20. Børge G. Nordestgaard
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  40. Sue A. Ingles
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  41. Christiane Maier
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Consortia

UKGPCS collaborators

APCB BioResource (Australian Prostate Cancer BioResource)

The IMPACT Study Steering Committee and Collaborators

Canary PASS Investigators

The Profile Study Steering Committee

The PRACTICAL Consortium

Corresponding authors

Correspondence to Roshan A. Karunamuni or Tyler M. Seibert.

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Conflict of interest

All authors declare no personal or financial conflicts of interest for the submitted work except as follows. CCF is a scientific consultant for CorTechs Labs, Inc. RE reports honorarium as a speaker for GU-ASCO meeting in San Francisco Jan 2016, support from Janssen, and honorarium as speaker for RMH-FR meeting Nov 2017. She reports honorarium as a speaker at the University of Chicago invited talk May 2018, and an educational honorarium by Bayer & Ipsen to attend GU Connect “Treatment sequencing for mCRPC patients within the changing landscape of mHSPC” at ESMO Barcelona, Sep 2019. She reports member of external Expert Committee on the Prostate Dx Advisory Panel. OAA received speaker’s honorarium from Lundbeck, and is a consultant for Healthlytix. AMD reports that he was a founder and holds equity in CorTechs Labs Inc., and serves on its Scientific Advisory Board. He is a member of the Scientific Advisory Board of Human Longevity, Inc., and the Mohn Medical Imaging and Visualization Centre. He received funding through research grants from GE Healthcare to UCSD. The terms of these arrangements have been reviewed by and approved by UCSD in accordance with its conflict of interest policies. TMS reports honoraria, outside of the present work, from: University of Rochester, Varian Medical Systems, Multimodal Imaging Servcies Corporation; and WebMD. He reports research funding from NIH/NBIB, U.S. Department of Defense, Radiological Society of North America, American Society for Radiation Oncology, and Varian Medical Systems.

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Karunamuni, R.A., Huynh-Le, MP., Fan, C.C. et al. Additional SNPs improve risk stratification of a polygenic hazard score for prostate cancer. Prostate Cancer Prostatic Dis 24, 532–541 (2021). https://doi.org/10.1038/s41391-020-00311-2

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