Additional SNPs improve risk stratification of a polygenic hazard score for prostate cancer.

Autor: Karunamuni RA; Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA. rakarunamuni@health.ucsd.edu., Huynh-Le MP; Radiation Oncology, George Washington University, Washington, DC, USA., Fan CC; Center for Human Development, University of California San Diego, La Jolla, CA, USA., Thompson W; Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA, USA., Eeles RA; The Institute of Cancer Research, London, SM2 5NG, UK.; Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK., Kote-Jarai Z; The Institute of Cancer Research, London, SM2 5NG, UK., Muir K; Division of Population Health, Health Services Research and Primary Care, University of Manchester, Oxford Road, Manchester, M13 9PL, UK.; Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK., Lophatananon A; Division of Population Health, Health Services Research and Primary Care, University of Manchester, Oxford Road, Manchester, M13 9PL, UK., Schleutker J; Institute of Biomedicine, University of Turku, Turku, Finland.; Department of Medical Genetics, Genomics, Laboratory Division, Turku University Hospital, PO Box 52, 20521, Turku, Finland., Pashayan N; Department of Applied Health Research, University College London, London, WC1E 7HB, UK.; Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Strangeways Laboratory, Worts Causeway, Cambridge, CB1 8RN, UK., Batra J; 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.; Translational Research Institute, Brisbane, QLD, 4102, Australia., Grönberg H; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, SE-171 77, Stockholm, Sweden., Walsh EI; Bristol Medical School, Department of Population Health Sciences, University of Bristol, Bristol, UK., Turner EL; Bristol Medical School, Department of Population Health Sciences, University of Bristol, Bristol, UK., Lane A; Bristol Medical School, Department of Population Health Sciences, University of Bristol, Bristol, UK.; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK., Martin RM; Bristol Medical School, Department of Population Health Sciences, University of Bristol, Bristol, UK.; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.; National Institute for Health Research (NIHR) Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, Bristol, UK., Neal DE; Nuffield Department of Surgical Sciences, University of Oxford, Room 6603, Level 6, John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU, UK.; Department of Oncology, University of Cambridge, Box 279, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, UK.; Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Cambridge, CB2 0RE, UK., Donovan JL; School of Social and Community Medicine, University of Bristol, Bristol, UK., Hamdy FC; Nuffield Department of Surgical Sciences, University of Oxford, Room 6603, Level 6, John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU, UK.; Faculty of Medical Science, University of Oxford, John Radcliffe Hospital, Oxford, UK., Nordestgaard BG; Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.; Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, 2200, Copenhagen, Denmark., Tangen CM; SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., MacInnis RJ; Cancer Epidemiology Division, Cancer Council Victoria, 615 St Kilda Road, Melbourne, VIC, 3004, Australia.; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Grattan Street, Parkville, VIC, 3010, Australia., Wolk A; Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, SE-171 77, Stockholm, Sweden.; Department of Surgical Sciences, Uppsala University, 75185, Uppsala, Sweden., Albanes D; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, 20892, USA., Haiman CA; 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., Travis RC; Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK., Stanford JL; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109-1024, USA.; Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, 98195, USA., Mucci LA; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, 02115, USA., West CML; 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., Nielsen SF; Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.; Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, 2200, Copenhagen, Denmark., Kibel AS; Division of Urologic Surgery, Brigham and Womens Hospital, 75 Francis Street, Boston, MA, 02115, USA., Wiklund F; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, SE-171 77, Stockholm, Sweden., Cussenot O; Sorbonne Universite, GRC n°5, AP-HP, Tenon Hospital, 4 rue de la Chine, F-75020, Paris, France.; CeRePP, Tenon Hospital, F-75020, Paris, France., Berndt SI; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, 20892, USA., Koutros S; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, 20892, USA., Sørensen KD; Department of Molecular Medicine, Aarhus University Hospital, Palle Juul-Jensen Boulevard 99, 8200, Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, DK-8200, Aarhus, Denmark., Cybulski C; International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, 70-115, Szczecin, Poland., Grindedal EM; Department of Medical Genetics, Oslo University Hospital, 0424, Oslo, Norway., Park JY; Department of Cancer Epidemiology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL, 33612, USA., Ingles SA; Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, 90015, USA., Maier C; Humangenetik Tuebingen, Paul-Ehrlich-Str 23, D-72076, Tuebingen, Germany., Hamilton RJ; Dept. of Surgical Oncology, Princess Margaret Cancer Centre, Toronto, ON, M5G 2M9, Canada.; Dept. of Surgery (Urology), University of Toronto, Toronto, ON, Canada., Rosenstein BS; 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.; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029-5674, USA., Vega A; Fundación Pública Galega Medicina Xenómica, Santiago de Compostela, 15706, Spain.; Instituto de Investigación Sanitaria de Santiago de Compostela, Santiago De Compostela, 15706, Spain.; Centro de Investigación en Red de Enfermedades Raras (CIBERER), Santiago De Compostela, Spain., Kogevinas M; ISGlobal, Barcelona, Spain.; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.; Universitat Pompeu Fabra (UPF), Barcelona, Spain.; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain., Penney KL; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA, 02184, USA., Teixeira MR; Department of Genetics, Portuguese Oncology Institute of Porto (IPO-Porto), 4200-072, Porto, Portugal.; Biomedical Sciences Institute (ICBAS), University of Porto, 4050-313, Porto, Portugal.; Cancer Genetics Group, IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), 4200-072, Porto, Portugal., Brenner H; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), D-69120, Heidelberg, Germany.; German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), D-69120, Heidelberg, Germany.; Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, 69120, Heidelberg, Germany., John EM; Departments of Epidemiology & Population Health and of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, 94304, USA., Kaneva R; Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical University of Sofia, Sofia, 2 Zdrave Str., 1431, Sofia, Bulgaria., Logothetis CJ; The University of Texas M. D. Anderson Cancer Center, Department of Genitourinary Medical Oncology, 1515 Holcombe Blvd., Houston, TX, 77030, USA., Neuhausen SL; Department of Population Sciences, Beckman Research Institute of the City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA., Razack A; Department of Surgery, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia., Newcomb LF; Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109-1024, USA.; Department of Urology, University of Washington, 1959 NE Pacific Street, Box 356510, Seattle, WA, 98195, USA., Gamulin M; Division of Medical Oncology, Urogenital Unit, Department of Oncology, University Hospital Centre Zagreb, University of Zagreb, School of Medicine, 10000, Zagreb, Croatia., Usmani N; Department of Oncology, Cross Cancer Institute, University of Alberta, 11560 University Avenue, Edmonton, AB, T6G 1Z2, Canada.; Division of Radiation Oncology, Cross Cancer Institute, 11560 University Avenue, Edmonton, AB, T6G 1Z2, Canada., Claessens F; Molecular Endocrinology Laboratory, Department of Cellular and Molecular Medicine, KU, Leuven, BE-3000, Belgium., Gago-Dominguez M; 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.; 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., Townsend PA; 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., Roobol MJ; Department of Urology, Erasmus University Medical Center, 3015 CE, Rotterdam, The Netherlands., Zheng W; Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, 2525 West End Avenue, Suite 800, Nashville, TN, 37232, USA., Mills IG; Center for Cancer Research and Cell Biology, Queen's University of Belfast, Belfast, UK., Andreassen OA; NORMENT, KG Jebsen Centre, Oslo University Hospital and University of Oslo, Oslo, Norway., Dale AM; Department of Radiology, University of California San Diego, La Jolla, CA, USA., Seibert TM; Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA. tseibert@ucsd.edu.; Department of Radiology, University of California San Diego, La Jolla, CA, USA. tseibert@ucsd.edu.; Department of Bioengineering, University of California San Diego, La Jolla, CA, USA. tseibert@ucsd.edu.
Jazyk: angličtina
Zdroj: Prostate cancer and prostatic diseases [Prostate Cancer Prostatic Dis] 2021 Jun; Vol. 24 (2), pp. 532-541. Date of Electronic Publication: 2021 Jan 08.
DOI: 10.1038/s41391-020-00311-2
Abstrakt: 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.
Databáze: MEDLINE
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