Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Dareng EO 1 , Tyrer JP 2 , Barnes DR 1 , Jones MR 3 , Yang X 1 , Aben KKH 4 Show all authors , Adank MA 5 , Agata S 6 , Andrulis IL 7 , Anton-Culver H 8 , Antonenkova NN 9 , Aravantinos G 10 , Arun BK 11 , Augustinsson A 12 , Balmaña J 13 , Bandera EV 14 , Barkardottir RB 15 , Barrowdale D 1 , Beckmann MW 16 , Beeghly-Fadiel A 17 , Benitez J 18 , Bermisheva M 19 , Bernardini MQ 20 , Bjorge L 21 , Black A 22 , Bogdanova NV 9 , Bonanni B 23 , Borg A 24 , Brenton JD 25 , Budzilowska A 26 , Butzow R 27 , Buys SS 28 , Cai H 17 , Caligo MA 29 , Campbell I 30 , Cannioto R 31 , Cassingham H 32 , Chang-Claude J 33 , Chanock SJ 34 , Chen K 35 , Chiew YE 36 , Chung WK 37 , Claes KBM 38 , Colonna S 28 , GEMO Study Collaborators , GC-HBOC Study Collaborators , EMBRACE Collaborators , Cook LS 39 , Couch FJ 40 , Daly MB 41 , Dao F 42 , Davies E 43 , de la Hoya M 44 , de Putter R 38 , Dennis J 1 , DePersia A 45 , Devilee P 46 , Diez O 47 , Ding YC 48 , Doherty JA 49 , Domchek SM 50 , Dörk T 51 , du Bois A 52 , Dürst M 53 , Eccles DM 54 , Eliassen HA 55 , Engel C 56 , Evans GD 57 , Fasching PA 16 , Flanagan JM 58 , Fortner RT 33 , Machackova E 59 , Friedman E 60 , Ganz PA 61 , Garber J 62 , Gensini F 63 , Giles GG 64 , Glendon G 7 , Godwin AK 65 , Goodman MT 66 , Greene MH 67 , Gronwald J 68 , OPAL Study Group , AOCS Group , Hahnen E 69 , Haiman CA 70 , Håkansson N 71 , Hamann U 72 , Hansen TVO 73 , Harris HR 74 , Hartman M 75 , Heitz F 52 , Hildebrandt MAT 76 , Høgdall E 77 , Høgdall CK 78 , Hopper JL 79 , Huang RY 80 , Huff C 76 , Hulick PJ 45 , Huntsman DG 81 , Imyanitov EN 82 , KConFab Investigators , HEBON Investigators , Isaacs C 83 , Jakubowska A 68 , James PA 84 , Janavicius R 85 , Jensen A 77 , Johannsson OT 86 , John EM 87 , Jones ME 88 , Kang D 89 , Karlan BY 90 , Karnezis A 91 , Kelemen LE 92 , Khusnutdinova E 19 , Kiemeney LA 4 , Kim BG 93 , Kjaer SK 77 , Komenaka I 94 , Kupryjanczyk J 26 , Kurian AW 87 , Kwong A 95 , Lambrechts D 96 , Larson MC 97 , Lazaro C 98 , Le ND 99 , Leslie G 1 , Lester J 90 , Lesueur F 100 , Levine DA 42 , Li L 35 , Li J 101 , Loud JT 67 , Lu KH 102 , Lubiński J 68 , Mai PL 103 , Manoukian S 104 , Marks JR 105 , Matsuno RK 106 , Matsuo K 107 , May T 20 , McGuffog L 1 , McLaughlin JR 108 , McNeish IA 109 , Mebirouk N 100 , Menon U 110 , Miller A 111 , Milne RL 64 , Minlikeeva A 112 , Modugno F 113 , Montagna M 6 , Moysich KB 112 , Munro E 114 , Nathanson KL 50 , Neuhausen SL 48 , Nevanlinna H 115 , Yie JNY 116 , Nielsen HR 117 , Nielsen FC 73 , Nikitina-Zake L 118 , Odunsi K 119 , Offit K 120 , Olah E 121 , Olbrecht S 122 , Olopade OI 123 , Olson SH 124 , Olsson H 12 , Osorio A 125 , Papi L 63 , Park SK 89 , Parsons MT 126 , Pathak H 65 , Pedersen IS 127 , Peixoto A 128 , Pejovic T 114 , Perez-Segura P 44 , Permuth JB 129 , Peshkin B 83 , Peterlongo P 130 , Piskorz A 25 , Prokofyeva D 131 , Radice P 132 , Rantala J 133 , Riggan MJ 134 , Risch HA 135 , Rodriguez-Antona C 18 , Ross E 136 , Rossing MA 74 , Runnebaum I 53 , Sandler DP 137 , Santamariña M 138 , Soucy P 139 , Schmutzler RK 69 , Setiawan VW 70 , Shan K 140 , Sieh W 141 , Simard J 142 , Singer CF 143 , Sokolenko AP 82 , Song H 144 , Southey MC 64 , Steed H 145 , Stoppa-Lyonnet D 146 , Sutphen R 147 , Swerdlow AJ 88 , Tan YY 143 , Teixeira MR 128 , Teo SH 148 , Terry KL 55 , Terry MB 149 , OCAC Consortium , CIMBA Consortium , Thomassen M 117 , Thompson PJ 66 , Thomsen LCV 21 , Thull DL 150 , Tischkowitz M 151 , Titus L 152 , Toland AE 153 , Torres D 72 , Trabert B 22 , Travis R 154 , Tung N 155 , Tworoger SS 55 , Valen E 21 , van Altena AM 4 , van der Hout AH 156 , Van Nieuwenhuysen E 122 , van Rensburg EJ 157 , Vega A 138 , Edwards DV 158 , Vierkant RA 97 , Wang F 159 , Wappenschmidt B 69 , Webb PM 160 , Weinberg CR 161 , Weitzel JN 162 , Wentzensen N 22 , White E 163 , Whittemore AS 87 , Winham SJ 97 , Wolk A 71 , Woo YL 164 , Wu AH 70 , Yan L 165 , Yannoukakos D 166 , Zavaglia KM 29 , Zheng W 17 , Ziogas A 8 , Zorn KK 103 , Kleibl Z 167 , Easton D 1 , Lawrenson K 3 , DeFazio A 36 , Sellers TA 168 , Ramus SJ 169 , Pearce CL 170 , Monteiro AN 129 , Cunningham J 171 , Goode EL 171 , Schildkraut JM 172 , Berchuck A 134 , Chenevix-Trench G 126 , Gayther SA 3 , Antoniou AC 1 , Pharoah PDP 173

Affiliations 

  • 1 University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge, UK
  • 2 University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Oncology, Cambridge, UK
  • 3 Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical Center, Los Angeles, CA, USA
  • 4 Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands
  • 5 The Netherlands Cancer Institute-Antoni van Leeuwenhoek hospital, Family Cancer Clinic, Amsterdam, The Netherlands
  • 6 Veneto Institute of Oncology IOV-IRCCS, Immunology and Molecular Oncology Unit, Padua, Italy
  • 7 Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Fred A. Litwin Center for Cancer Genetics, Toronto, ON, Canada
  • 8 University of California Irvine, Department of Epidemiology, Genetic Epidemiology Research Institute, Irvine, CA, USA
  • 9 N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus
  • 10 'Agii Anargiri' Cancer Hospital, Athens, Greece
  • 11 University of Texas MD Anderson Cancer Center, Department of Breast Medical Oncology, Houston, TX, USA
  • 12 Lund University, Department of Cancer Epidemiology, Clinical Sciences, Lund, Sweden
  • 13 Vall d'Hebron Institute of Oncology, Hereditary cancer Genetics Group, Barcelona, Spain
  • 14 Rutgers Cancer Institute of New Jersey, Cancer Prevention and Control Program, New Brunswick, NJ, USA
  • 15 Landspitali University Hospital, Department of Pathology, Reykjavik, Iceland
  • 16 University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, Erlangen, Germany
  • 17 Vanderbilt University School of Medicine, Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
  • 18 Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain
  • 19 Ufa Federal Research Centre of the Russian Academy of Sciences, Institute of Biochemistry and Genetics, Ufa, Russia
  • 20 Princess Margaret Hospital, Division of Gynecologic Oncology, University Health Network, Toronto, ON, Canada
  • 21 Haukeland University Hospital, Department of Obstetrics and Gynecology, Bergen, Norway
  • 22 National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA
  • 23 IEO, European Institute of Oncology IRCCS, Division of Cancer Prevention and Genetics, Milan, Italy
  • 24 Lund University and Skåne University Hospital, Department of Oncology, Lund, Sweden
  • 25 Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
  • 26 Maria Sklodowska-Curie National Research Institute of Oncology, Department of Pathology and Laboratory Diagnostics, Warsaw, Poland
  • 27 University of Helsinki, Department of Pathology, Helsinki University Hospital, Helsinki, Finland
  • 28 Huntsman Cancer Institute, Department of Medicine, Salt Lake City, UT, USA
  • 29 University Hospital, SOD Genetica Molecolare, Pisa, Italy
  • 30 Peter MacCallum Cancer Center, Melbourne, VIC, Australia
  • 31 Roswell Park Cancer Institute, Cancer Pathology & Prevention, Division of Cancer Prevention and Population Sciences, Buffalo, NY, USA
  • 32 Division of Human Genetics, The Ohio State University, Department of Internal Medicine, Columbus, OH, USA
  • 33 German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany
  • 34 National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA
  • 35 Tianjin Medical University Cancer Institute and Hospital, Department of Epidemiology, Tianjin, China
  • 36 The University of Sydney, Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, NSW, Australia
  • 37 Columbia University, Departments of Pediatrics and Medicine, New York, NY, USA
  • 38 Ghent University, Centre for Medical Genetics, Gent, Belgium
  • 39 University of New Mexico, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
  • 40 Mayo Clinic, Department of Laboratory Medicine and Pathology, Rochester, MN, USA
  • 41 Fox Chase Cancer Center, Department of Clinical Genetics, Philadelphia, PA, USA
  • 42 Memorial Sloan Kettering Cancer Center, Gynecology Service, Department of Surgery, New York, NY, USA
  • 43 Cambridge, Cambridge, UK
  • 44 CIBERONC, Hospital Clinico San Carlos, IdISSC (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos), Molecular Oncology Laboratory, Madrid, Spain
  • 45 NorthShore University Health System, Center for Medical Genetics, Evanston, IL, USA
  • 46 Leiden University Medical Center, Department of Pathology, Leiden, The Netherlands
  • 47 Vall dHebron Institute of Oncology (VHIO), Oncogenetics Group, Barcelona, Spain
  • 48 Beckman Research Institute of City of Hope, Department of Population Sciences, Duarte, CA, USA
  • 49 University of Utah, Huntsman Cancer Institute, Department of Population Health Sciences, Salt Lake City, UT, USA
  • 50 University of Pennsylvania, Basser Center for BRCA, Abramson Cancer Center, Philadelphia, PA, USA
  • 51 Hannover Medical School, Gynaecology Research Unit, Hannover, Germany
  • 52 Ev. Kliniken Essen-Mitte (KEM), Department of Gynecology and Gynecologic Oncology, Essen, Germany
  • 53 Jena University Hospital-Friedrich Schiller University, Department of Gynaecology, Jena, Germany
  • 54 University of Southampton, Faculty of Medicine, Southampton, UK
  • 55 Harvard T.H. Chan School of Public Health, Department of Epidemiology, Boston, MA, USA
  • 56 University of Leipzig, Institute for Medical Informatics, Statistics and Epidemiology, Leipzig, Germany
  • 57 University of Manchester, Manchester Academic Health Science Centre, Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester, UK
  • 58 Imperial College London, Division of Cancer and Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, London, UK
  • 59 Masaryk Memorial Cancer Institute, Department of Cancer Epidemiology and Genetics, Brno, Czech Republic
  • 60 Chaim Sheba Medical Center, The Susanne Levy Gertner Oncogenetics Unit, Ramat Gan, Israel
  • 61 Jonsson Comprehensive Cancer Centre, UCLA, Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research, Los Angeles, CA, USA
  • 62 Dana-Farber Cancer Institute, Cancer Risk and Prevention Clinic, Boston, MA, USA
  • 63 University of Florence, Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', Medical Genetics Unit, Florence, Italy
  • 64 Cancer Council Victoria, Cancer Epidemiology Division, Melbourne, VIC, Australia
  • 65 University of Kansas Medical Center, Department of Pathology and Laboratory Medicine, Kansas City, KS, USA
  • 66 Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, Cancer Prevention and Genetics Program, Los Angeles, CA, USA
  • 67 National Cancer Institute, Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA
  • 68 Pomeranian Medical University, Department of Genetics and Pathology, Szczecin, Poland
  • 69 Faculty of Medicine and University Hospital Cologne, University of Cologne, Center for Familial Breast and Ovarian Cancer, Cologne, Germany
  • 70 University of Southern California, Department of Preventive Medicine, Keck School of Medicine, Los Angeles, CA, USA
  • 71 Karolinska Institutet, Institute of Environmental Medicine, Stockholm, Sweden
  • 72 German Cancer Research Center (DKFZ), Molecular Genetics of Breast Cancer, Heidelberg, Germany
  • 73 Rigshospitalet, Copenhagen University Hospital, Department of Clinical Genetics, Copenhagen, Denmark
  • 74 Fred Hutchinson Cancer Research Center, Program in Epidemiology, Division of Public Health Sciences, Seattle, WA, USA
  • 75 National University of Singapore and National University Health System, Saw Swee Hock School of Public Health, Singapore, Singapore
  • 76 University of Texas MD Anderson Cancer Center, Department of Epidemiology, Houston, TX, USA
  • 77 Danish Cancer Society Research Center, Department of Virus, Lifestyle and Genes, Copenhagen, Denmark
  • 78 University of Copenhagen, Department of Gynaecology, Rigshospitalet, Copenhagen, Denmark
  • 79 The University of Melbourne, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Melbourne, VIC, Australia
  • 80 Roswell Park Cancer Institute, Center For Immunotherapy, Buffalo, NY, USA
  • 81 BC Cancer, Vancouver General Hospital, and University of British Columbia, British Columbia's Ovarian Cancer Research (OVCARE) Program, Vancouver, BC, Canada
  • 82 N.N. Petrov Institute of Oncology, St. Petersburg, Russia
  • 83 Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA
  • 84 The University of Melbourne, Sir Peter MacCallum Department of Oncology, Melbourne, VIC, Australia
  • 85 Vilnius University Hospital Santariskiu Clinics, Hematology, oncology and transfusion medicine center, Dept. of Molecular and Regenerative Medicine, Vilnius, Lithuania
  • 86 Landspitali University Hospital, Department of Oncology, Reykjavik, Iceland
  • 87 Stanford University School of Medicine, Department of Epidemiology & Population Health, Stanford, CA, USA
  • 88 The Institute of Cancer Research, Division of Genetics and Epidemiology, London, UK
  • 89 Seoul National University College of Medicine, Department of Preventive Medicine, Seoul, Korea
  • 90 University of California at Los Angeles, David Geffen School of Medicine, Department of Obstetrics and Gynecology, Los Angeles, CA, USA
  • 91 UC Davis Medical Center, Department of Pathology and Laboratory Medicine, Sacramento, CA, USA
  • 92 Medical University of South Carolina, Hollings Cancer Center, Charleston, SC, USA
  • 93 Sungkyunkwan University School of Medicine, Department of Obstetrics and Gynecology, Samsung Medical Center, Seoul, Korea
  • 94 City of Hope Clinical Cancer Genetics Community Research Network, Duarte, CA, USA
  • 95 Cancer Genetics Centre, Hong Kong Hereditary Breast Cancer Family Registry, Happy Valley, Hong Kong
  • 96 VIB Center for Cancer Biology, Leuven, Belgium
  • 97 Mayo Clinic, Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Rochester, MN, USA
  • 98 ONCOBELL-IDIBELL-IGTP, Catalan Institute of Oncology, CIBERONC, Hereditary Cancer Program, Barcelona, Spain
  • 99 BC Cancer, Cancer Control Research, Vancouver, BC, Canada
  • 100 Institut Curie, Paris, France
  • 101 Genome Institute of Singapore, Human Genetics Division, Singapore, Singapore
  • 102 University of Texas MD Anderson Cancer Center, Department of Gynecologic Oncology and Clinical Cancer Genetics Program, Houston, TX, USA
  • 103 Magee-Womens Hospital, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
  • 104 Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Unit of Medical Genetics, Department of Medical Oncology and Hematology, Milan, Italy
  • 105 Duke University Hospital, Department of Surgery, Durham, NC, USA
  • 106 University of Hawaii Cancer Center, Cancer Epidemiology Program, Honolulu, HI, USA
  • 107 Aichi Cancer Center Research Institute, Division of Cancer Epidemiology and Prevention, Nagoya, Japan
  • 108 Samuel Lunenfeld Research Institute, Public Health Ontario, Toronto, ON, Canada
  • 109 Imperial College London, Division of Cancer and Ovarian Cancer Action Research Centre, Department Surgery & Cancer, London, UK
  • 110 University College London, MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, London, UK
  • 111 Roswell Park Cancer Institute, NRG Oncology, Statistics and Data Management Center, Buffalo, NY, USA
  • 112 Roswell Park Cancer Institute, Division of Cancer Prevention and Control, Buffalo, NY, USA
  • 113 Magee-Womens Research Institute and Hillman Cancer Center, Womens Cancer Research Center, Pittsburgh, PA, USA
  • 114 Oregon Health & Science University, Department of Obstetrics and Gynecology, Portland, OR, USA
  • 115 University of Helsinki, Department of Obstetrics and Gynecology, Helsinki University Hospital, Helsinki, Finland
  • 116 National Cancer Centre, Cancer Genetics Service, Singapore, Singapore
  • 117 Odense University Hospital, Department of Clinical Genetics, Odence C, Denmark
  • 118 Latvian Biomedical Research and Study Centre, Riga, Latvia
  • 119 Roswell Park Cancer Institute, Department of Gynecologic Oncology, Buffalo, NY, USA
  • 120 Memorial Sloan Kettering Cancer Center, Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, New York, NY, USA
  • 121 National Institute of Oncology, Department of Molecular Genetics, Budapest, Hungary
  • 122 University Hospitals Leuven, Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, Leuven, Belgium
  • 123 The University of Chicago, Center for Clinical Cancer Genetics, Chicago, IL, USA
  • 124 Memorial Sloan-Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY, USA
  • 125 Spanish National Cancer Research Centre (CNIO), Human Cancer Genetics Programme, Madrid, Spain
  • 126 QIMR Berghofer Medical Research Institute, Department of Genetics and Computational Biology, Brisbane, QLD, Australia
  • 127 Aalborg University Hospital, Molecular Diagnostics, Aalborg, Denmark
  • 128 Portuguese Oncology Institute, Department of Genetics, Porto, Portugal
  • 129 Moffitt Cancer Center, Department of Cancer Epidemiology, Tampa, FL, USA
  • 130 IFOM-the FIRC Institute of Molecular Oncology, Genome Diagnostics Program, Milan, Italy
  • 131 Bashkir State University, Department of Genetics and Fundamental Medicine, Ufa, Russia
  • 132 Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Milan, Italy
  • 133 Karolinska Institutet, Clinical Genetics, Stockholm, Sweden
  • 134 Duke University Hospital, Department of Gynecologic Oncology, Durham, NC, USA
  • 135 Yale School of Public Health, Chronic Disease Epidemiology, New Haven, CT, USA
  • 136 Fox Chase Cancer Center, Population Studies Facility, Philadelphia, PA, USA
  • 137 National Institute of Environmental Health Sciences, NIH, Epidemiology Branch, Research Triangle Park, NC, USA
  • 138 Centro de Investigación en Red de Enfermedades Raras (CIBERER), Madrid, Spain
  • 139 Centre Hospitalier Universitaire de Québec - Université Laval Research Center, Genomics Center, Québec City, QC, Canada
  • 140 Hebei Medical University, Fourth Hospital, Department of Obstetrics and Gynaecology, Shijiazhuang, China
  • 141 Icahn School of Medicine at Mount Sinai, Department of Population Health Science and Policy, New York, NY, USA
  • 142 Centre Hospitalier Universitaire de Québec-Université Laval Research Center, Genomic Center, Québec City, QC, Canada
  • 143 Medical University of Vienna, Dept of OB/GYN and Comprehensive Cancer Center, Vienna, Austria
  • 144 University of Cambridge, Department of Public Health and Primary Care, Cambridge, UK
  • 145 Royal Alexandra Hospital, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Edmonton, AB, Canada
  • 146 INSERM U830, Department of Tumour Biology, Paris, France
  • 147 University of South Florida, Epidemiology Center, College of Medicine, Tampa, FL, USA
  • 148 Cancer Research Malaysia, Breast Cancer Research Programme, Subang Jaya, Selangor, Malaysia
  • 149 Columbia University, Department of Epidemiology, Mailman School of Public Health, New York, NY, USA
  • 150 Magee-Womens Hospital, University of Pittsburgh School of Medicine, Department of Medicine, Pittsburgh, PA, USA
  • 151 McGill University, Program in Cancer Genetics, Departments of Human Genetics and Oncology, Montréal, QC, Canada
  • 152 Dartmouth College, Geisel School of Medicine, Hanover, NH, USA
  • 153 The Ohio State University, Department of Cancer Biology and Genetics, Columbus, OH, USA
  • 154 University of Oxford, Cancer Epidemiology Unit, Oxford, UK
  • 155 Beth Israel Deaconess Medical Center, Department of Medical Oncology, Boston, MA, USA
  • 156 University Medical Center Groningen, University Groningen, Department of Genetics, Groningen, The Netherlands
  • 157 University of Pretoria, Department of Genetics, Arcadia, South Africa
  • 158 Vanderbilt University Medical Center, Division of Quantitative Sciences, Department of Obstetrics and Gynecology, Department of Biomedical Sciences, Women's Health Research, Nashville, TN, USA
  • 159 Duke Cancer Institute, Cancer Control and Population Sciences, Durham, NC, USA
  • 160 QIMR Berghofer Medical Research Institute, Population Health Department, Brisbane, QLD, Australia
  • 161 National Institute of Environmental Health Sciences, NIH, Biostatistics and Computational Biology Branch, Research Triangle Park, NC, USA
  • 162 City of Hope, Clinical Cancer Genomics, Duarte, CA, USA
  • 163 University of Washington, Department of Epidemiology, Seattle, WA, USA
  • 164 University of Malaya, Department of Obstetrics and Gynaecology, University of Malaya Medical Centre, Kuala Lumpur, Malaysia
  • 165 Hebei Medical University, Fourth Hospital, Department of Molecular Biology, Shijiazhuang, China
  • 166 National Centre for Scientific Research 'Demokritos', Molecular Diagnostics Laboratory, INRASTES, Athens, Greece
  • 167 Institute of Biochemistry and Experimental Oncology, First Faculty od Medicine, Charles University, Prague, Czech Republic
  • 168 Royal Pass Road, Tampa, FL, USA
  • 169 University of NSW Sydney, School of Women's and Children's Health, Faculty of Medicine, Sydney, NSW, Australia
  • 170 University of Michigan School of Public Health, Department of Epidemiology, Ann Arbor, MI, USA
  • 171 Mayo Clinic, Department of Health Science Research, Division of Epidemiology, Rochester, MN, USA
  • 172 Emory University, Department of Epidemiology, Rollins School of Public Health, Atlanta, GA, USA
  • 173 University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge, UK. [email protected]
Eur J Hum Genet, 2022 Jan 14.
PMID: 35027648 DOI: 10.1038/s41431-021-00987-7

Abstract

Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.

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

Similar publications