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    European journal of human genetics : EJHG. 2022 Jan 14. doi: 10.1038/s41431-021-00987-7. pii: 10.1038/s41431-021-00987-7
    Polygenic risk modeling for prediction of epithelial ovarian cancer risk.
    Dareng EO1,  Tyrer JP2,  Barnes DR3,  Jones MR4,  Yang X5,  Aben KKH6,  Adank MA7,  Agata S8,  Andrulis IL9,  Anton-Culver H10,  Antonenkova NN11,  Aravantinos G12,  Arun BK13,  Augustinsson A14,  Balmaña J15,  Bandera EV16,  Barkardottir RB17,  Barrowdale D18,  Beckmann MW19,  Beeghly-Fadiel A20,  Benitez J21,  Bermisheva M22,  Bernardini MQ23,  Bjorge L24,  Black A25,  Bogdanova NV26,  Bonanni B27,  Borg A28,  Brenton JD29,  Budzilowska A30,  Butzow R31,  Buys SS32,  Cai H33,  Caligo MA34,  Campbell I35,  Cannioto R36,  Cassingham H37,  Chang-Claude J38,  Chanock SJ39,  Chen K40,  Chiew YE41,  Chung WK42,  Claes KBM43,  Colonna S44,  Cook LS45,  Couch FJ46,  Daly MB47,  Dao F48,  Davies E49,  de la Hoya M50,  de Putter R51,  Dennis J52,  DePersia A53,  Devilee P54,  Diez O55,  Ding YC56,  Doherty JA57,  Domchek SM58,  Dörk T59,  du Bois A60,  Dürst M61,  Eccles DM62,  Eliassen HA63,  Engel C64,  Evans GD65,  Fasching PA66,  Flanagan JM67,  Fortner RT68,  Machackova E69,  Friedman E70,  Ganz PA71,  Garber J72,  Gensini F73,  Giles GG74,  Glendon G75,  Godwin AK76,  Goodman MT77,  Greene MH78,  Gronwald J79,  Hahnen E80,  Haiman CA81,  Håkansson N82,  Hamann U83,  Hansen TVO84,  Harris HR85,  Hartman M86,  Heitz F87,  Hildebrandt MAT88,  Høgdall E89,  Høgdall CK90,  Hopper JL91,  Huang RY92,  Huff C93,  Hulick PJ94,  Huntsman DG95,  Imyanitov EN96,  Isaacs C97,  Jakubowska A98,  James PA99,  Janavicius R100,  Jensen A101,  Johannsson OT102,  John EM103,  Jones ME104,  Kang D105,  Karlan BY106,  Karnezis A107,  Kelemen LE108,  Khusnutdinova E109,  Kiemeney LA110,  Kim BG111,  Kjaer SK112,  Komenaka I113,  Kupryjanczyk J114,  Kurian AW115,  Kwong A116,  Lambrechts D117,  Larson MC118,  Lazaro C119,  Le ND120,  Leslie G121,  Lester J122,  Lesueur F123,  Levine DA124,  Li L125,  Li J126,  Loud JT127,  Lu KH128,  Lubiński J129,  Mai PL130,  Manoukian S131,  Marks JR132,  Matsuno RK133,  Matsuo K134,  May T135,  McGuffog L136,  McLaughlin JR137,  McNeish IA138,  Mebirouk N139,  Menon U140,  Miller A141,  Milne RL142,  Minlikeeva A143,  Modugno F144,  Montagna M145,  Moysich KB146,  Munro E147,  Nathanson KL148,  Neuhausen SL149,  Nevanlinna H150,  Yie JNY151,  Nielsen HR152,  Nielsen FC153,  Nikitina-Zake L154,  Odunsi K155,  Offit K156,  Olah E157,  Olbrecht S158,  Olopade OI159,  Olson SH160,  Olsson H161,  Osorio A162,  Papi L163,  Park SK164,  Parsons MT165,  Pathak H166,  Pedersen IS167,  Peixoto A168,  Pejovic T169,  Perez-Segura P170,  Permuth JB171,  Peshkin B172,  Peterlongo P173,  Piskorz A174,  Prokofyeva D175,  Radice P176,  Rantala J177,  Riggan MJ178,  Risch HA179,  Rodriguez-Antona C180,  Ross E181,  Rossing MA182,  Runnebaum I183,  Sandler DP184,  Santamariña M185,  Soucy P186,  Schmutzler RK187,  Setiawan VW188,  Shan K189,  Sieh W190,  Simard J191,  Singer CF192,  Sokolenko AP193,  Song H194,  Southey MC195,  Steed H196,  Stoppa-Lyonnet D197,  Sutphen R198,  Swerdlow AJ199,  Tan YY200,  Teixeira MR201,  Teo SH202,  Terry KL203,  Terry MB204,  Thomassen M205,  Thompson PJ206,  Thomsen LCV207,  Thull DL208,  Tischkowitz M209,  Titus L210,  Toland AE211,  Torres D212,  Trabert B213,  Travis R214,  Tung N215,  Tworoger SS216,  Valen E217,  van Altena AM218,  van der Hout AH219,  Van Nieuwenhuysen E220,  van Rensburg EJ221,  Vega A222,  Edwards DV223,  Vierkant RA224,  Wang F225,  Wappenschmidt B226,  Webb PM227,  Weinberg CR228,  Weitzel JN229,  Wentzensen N230,  White E231,  Whittemore AS232,  Winham SJ233,  Wolk A234,  Woo YL235,  Wu AH236,  Yan L237,  Yannoukakos D238,  Zavaglia KM239,  Zheng W240,  Ziogas A241,  Zorn KK242,  Kleibl Z243,  Easton D244,  Lawrenson K245,  DeFazio A246,  Sellers TA247,  Ramus SJ248,  Pearce CL249,  Monteiro AN250,  Cunningham J251,  Goode EL252,  Schildkraut JM253,  Berchuck A254,  Chenevix-Trench G255,  Gayther SA256,  Antoniou AC257,  Pharoah PDP258
    Collaborators
    Lesueur F Mebirouk N Engel C Schmutzler RK Barrowdale D Davies E Eccles DM Evans DG Chenevix-Trench G Adank MA Devilee P van der Hout AH Dareng EO Tyrer JP Jones MR Aben KKH Anton-Culver H Antonenkova NN Aravantinos G Beckmann MW Beeghly-Fadiel A Benitez J Bermisheva M Bernardini MQ Bjorge L Bogdanova NV Brenton JD Budzilowska A Butzow R Cai H Campbell I Cannioto R Chang-Claude J Chanock SJ Chen K Chiew YE Cook LS Dao F Dennis J Doherty JA Dörk T du Bois A Dürst M Eccles DM Eliassen HA Fasching PA Flanagan JM Fortner RT Giles GG Goodman MT Gronwald J Haiman CA Håkansson N Harris HR Heitz F Hildebrandt MAT Høgdall E Høgdall CK Huang RY Huff C Huntsman DG Jakubowska A Jensen A Jones ME Kang D Karlan BY Karnezis A Kelemen LE Khusnutdinova E Kiemeney LA Kim BG Kjaer SK Kupryjanczyk J Lambrechts D Larson MC Le ND Lester J Levine DA Lu KH Lubiński J Marks JR Matsuno RK Matsuo K May T McLaughlin JR McNeish IA Milne RL Minlikeeva A Modugno F Moysich KB Munro E Nevanlinna H Odunsi K Olbrecht S Olson SH Olsson H Osorio A Park SK Pejovic T Permuth JB Piskorz A Prokofyeva D Riggan MJ Risch HA Rodriguez-Antona C Rossing MA Runnebaum I Sandler DP Setiawan VW Shan K Sieh W Song H Southey MC Steed H Sutphen R Swerdlow AJ Teo SH Terry KL Thompson PJ Thomsen LCV Titus L Trabert B Travis R Tworoger SS Valen E van Altena AM Van Nieuwenhuysen E Edwards DV Vierkant RA Wang F Webb PM Weinberg CR Wentzensen N White E Whittemore AS Winham SJ Wolk A Woo YL Wu AH Yan L Yannoukakos D Zheng W Ziogas A Lawrenson K deFazio A Ramus SJ Pearce CL Monteiro AN Cunningham JM Goode EL Schildkraut JM Berchuck A Gayther SA Pharoah PDP Barnes DR Yang X Adank MA Agata S Andrulis IL Arun BK Augustinsson A Balmaña J Barkardottir RB Barrowdale D Bonanni B Borg A Buys SS Caligo MA Cassingham H Chung WK Claes KBM Colonna S Couch FJ Daly MB Davies E de la Hoya M de Putter R DePersia A Devilee P Diez O Ding YC Domchek SM Eccles DM Engel C Evans DG Machackova E Friedman E Ganz PA Garber J Gensini F Glendon G Godwin AK Greene MH Hahnen E Hamann U Hansen TVO Hartman M Hopper JL Hulick PJ Imyanitov EN Isaacs C James PA Janavicius R Johannsson OT John EM Komenaka I Kurian AW Kwong A Lazaro C Leslie G Lesueur F Li J Loud JT Mai PL Manoukian S McGuffog L Mebirouk N Miller A Montagna M Nathanson KL Neuhausen SL Yie JNY Nielsen HR Nikitina-Zake L Offit K Olah E Olopade OI Papi L Parsons MT Pathak H Pedersen IS Peixoto A Perez-Segura P Peshkin B Peterlongo P Radice P Rantala J Ross E Santamariña M Soucy P Schmutzler RK Simard J Singer CF Sokolenko AP Stoppa-Lyonnet D Tan YY Teixeira MR Terry MB Thomassen M Thull DL Tischkowitz M Toland AE Torres D Tung N van der Hout AH van Rensburg EJ Vega A Wappenschmidt B Weitzel JN Zavaglia KM Zorn KK Sellers TA Chenevix-Trench G Antoniou AC
    Author information
    1University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge, UK.
    2University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Oncology, Cambridge, UK.
    3University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge, UK.
    4Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
    5University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge, UK.
    6Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
    7The Netherlands Cancer Institute-Antoni van Leeuwenhoek hospital, Family Cancer Clinic, Amsterdam, The Netherlands.
    8Veneto Institute of Oncology IOV-IRCCS, Immunology and Molecular Oncology Unit, Padua, Italy.
    9Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Fred A. Litwin Center for Cancer Genetics, Toronto, ON, Canada.
    10University of California Irvine, Department of Epidemiology, Genetic Epidemiology Research Institute, Irvine, CA, USA.
    11N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus.
    12'Agii Anargiri' Cancer Hospital, Athens, Greece.
    13University of Texas MD Anderson Cancer Center, Department of Breast Medical Oncology, Houston, TX, USA.
    14Lund University, Department of Cancer Epidemiology, Clinical Sciences, Lund, Sweden.
    15Vall d'Hebron Institute of Oncology, Hereditary cancer Genetics Group, Barcelona, Spain.
    16Rutgers Cancer Institute of New Jersey, Cancer Prevention and Control Program, New Brunswick, NJ, USA.
    17Landspitali University Hospital, Department of Pathology, Reykjavik, Iceland.
    18University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge, UK.
    19University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, Erlangen, Germany.
    20Vanderbilt University School of Medicine, Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
    21Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain.
    22Ufa Federal Research Centre of the Russian Academy of Sciences, Institute of Biochemistry and Genetics, Ufa, Russia.
    23Princess Margaret Hospital, Division of Gynecologic Oncology, University Health Network, Toronto, ON, Canada.
    24Haukeland University Hospital, Department of Obstetrics and Gynecology, Bergen, Norway.
    25National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA.
    26N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus.
    27IEO, European Institute of Oncology IRCCS, Division of Cancer Prevention and Genetics, Milan, Italy.
    28Lund University and Skåne University Hospital, Department of Oncology, Lund, Sweden.
    29Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
    30Maria Sklodowska-Curie National Research Institute of Oncology, Department of Pathology and Laboratory Diagnostics, Warsaw, Poland.
    31University of Helsinki, Department of Pathology, Helsinki University Hospital, Helsinki, Finland.
    32Huntsman Cancer Institute, Department of Medicine, Salt Lake City, UT, USA.
    33Vanderbilt University School of Medicine, Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
    34University Hospital, SOD Genetica Molecolare, Pisa, Italy.
    35Peter MacCallum Cancer Center, Melbourne, VIC, Australia.
    36Roswell Park Cancer Institute, Cancer Pathology & Prevention, Division of Cancer Prevention and Population Sciences, Buffalo, NY, USA.
    37Division of Human Genetics, The Ohio State University, Department of Internal Medicine, Columbus, OH, USA.
    38German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany.
    39National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA.
    40Tianjin Medical University Cancer Institute and Hospital, Department of Epidemiology, Tianjin, China.
    41The University of Sydney, Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, NSW, Australia.
    42Columbia University, Departments of Pediatrics and Medicine, New York, NY, USA.
    43Ghent University, Centre for Medical Genetics, Gent, Belgium.
    44Huntsman Cancer Institute, Department of Medicine, Salt Lake City, UT, USA.
    45University of New Mexico, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
    46Mayo Clinic, Department of Laboratory Medicine and Pathology, Rochester, MN, USA.
    47Fox Chase Cancer Center, Department of Clinical Genetics, Philadelphia, PA, USA.
    48Memorial Sloan Kettering Cancer Center, Gynecology Service, Department of Surgery, New York, NY, USA.
    49Cambridge, Cambridge, UK.
    50CIBERONC, Hospital Clinico San Carlos, IdISSC (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos), Molecular Oncology Laboratory, Madrid, Spain.
    51Ghent University, Centre for Medical Genetics, Gent, Belgium.
    52University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge, UK.
    53NorthShore University Health System, Center for Medical Genetics, Evanston, IL, USA.
    54Leiden University Medical Center, Department of Pathology, Leiden, The Netherlands.
    55Vall dHebron Institute of Oncology (VHIO), Oncogenetics Group, Barcelona, Spain.
    56Beckman Research Institute of City of Hope, Department of Population Sciences, Duarte, CA, USA.
    57University of Utah, Huntsman Cancer Institute, Department of Population Health Sciences, Salt Lake City, UT, USA.
    58University of Pennsylvania, Basser Center for BRCA, Abramson Cancer Center, Philadelphia, PA, USA.
    59Hannover Medical School, Gynaecology Research Unit, Hannover, Germany.
    60Ev. Kliniken Essen-Mitte (KEM), Department of Gynecology and Gynecologic Oncology, Essen, Germany.
    61Jena University Hospital-Friedrich Schiller University, Department of Gynaecology, Jena, Germany.
    62University of Southampton, Faculty of Medicine, Southampton, UK.
    63Harvard T.H. Chan School of Public Health, Department of Epidemiology, Boston, MA, USA.
    64University of Leipzig, Institute for Medical Informatics, Statistics and Epidemiology, Leipzig, Germany.
    65University 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.
    66University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, Erlangen, Germany.
    67Imperial College London, Division of Cancer and Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, London, UK.
    68German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany.
    69Masaryk Memorial Cancer Institute, Department of Cancer Epidemiology and Genetics, Brno, Czech Republic.
    70Chaim Sheba Medical Center, The Susanne Levy Gertner Oncogenetics Unit, Ramat Gan, Israel.
    71Jonsson Comprehensive Cancer Centre, UCLA, Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research, Los Angeles, CA, USA.
    72Dana-Farber Cancer Institute, Cancer Risk and Prevention Clinic, Boston, MA, USA.
    73University of Florence, Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', Medical Genetics Unit, Florence, Italy.
    74Cancer Council Victoria, Cancer Epidemiology Division, Melbourne, VIC, Australia.
    75Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Fred A. Litwin Center for Cancer Genetics, Toronto, ON, Canada.
    76University of Kansas Medical Center, Department of Pathology and Laboratory Medicine, Kansas City, KS, USA.
    77Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, Cancer Prevention and Genetics Program, Los Angeles, CA, USA.
    78National Cancer Institute, Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA.
    79Pomeranian Medical University, Department of Genetics and Pathology, Szczecin, Poland.
    80Faculty of Medicine and University Hospital Cologne, University of Cologne, Center for Familial Breast and Ovarian Cancer, Cologne, Germany.
    81University of Southern California, Department of Preventive Medicine, Keck School of Medicine, Los Angeles, CA, USA.
    82Karolinska Institutet, Institute of Environmental Medicine, Stockholm, Sweden.
    83German Cancer Research Center (DKFZ), Molecular Genetics of Breast Cancer, Heidelberg, Germany.
    84Rigshospitalet, Copenhagen University Hospital, Department of Clinical Genetics, Copenhagen, Denmark.
    85Fred Hutchinson Cancer Research Center, Program in Epidemiology, Division of Public Health Sciences, Seattle, WA, USA.
    86National University of Singapore and National University Health System, Saw Swee Hock School of Public Health, Singapore, Singapore.
    87Ev. Kliniken Essen-Mitte (KEM), Department of Gynecology and Gynecologic Oncology, Essen, Germany.
    88University of Texas MD Anderson Cancer Center, Department of Epidemiology, Houston, TX, USA.
    89Danish Cancer Society Research Center, Department of Virus, Lifestyle and Genes, Copenhagen, Denmark.
    90University of Copenhagen, Department of Gynaecology, Rigshospitalet, Copenhagen, Denmark.
    91The University of Melbourne, Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Melbourne, VIC, Australia.
    92Roswell Park Cancer Institute, Center For Immunotherapy, Buffalo, NY, USA.
    93University of Texas MD Anderson Cancer Center, Department of Epidemiology, Houston, TX, USA.
    94NorthShore University Health System, Center for Medical Genetics, Evanston, IL, USA.
    95BC Cancer, Vancouver General Hospital, and University of British Columbia, British Columbia's Ovarian Cancer Research (OVCARE) Program, Vancouver, BC, Canada.
    96N.N. Petrov Institute of Oncology, St. Petersburg, Russia.
    97Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
    98Pomeranian Medical University, Department of Genetics and Pathology, Szczecin, Poland.
    99The University of Melbourne, Sir Peter MacCallum Department of Oncology, Melbourne, VIC, Australia.
    100Vilnius University Hospital Santariskiu Clinics, Hematology, oncology and transfusion medicine center, Dept. of Molecular and Regenerative Medicine, Vilnius, Lithuania.
    101Danish Cancer Society Research Center, Department of Virus, Lifestyle and Genes, Copenhagen, Denmark.
    102Landspitali University Hospital, Department of Oncology, Reykjavik, Iceland.
    103Stanford University School of Medicine, Department of Epidemiology & Population Health, Stanford, CA, USA.
    104The Institute of Cancer Research, Division of Genetics and Epidemiology, London, UK.
    105Seoul National University College of Medicine, Department of Preventive Medicine, Seoul, Korea.
    106University of California at Los Angeles, David Geffen School of Medicine, Department of Obstetrics and Gynecology, Los Angeles, CA, USA.
    107UC Davis Medical Center, Department of Pathology and Laboratory Medicine, Sacramento, CA, USA.
    108Medical University of South Carolina, Hollings Cancer Center, Charleston, SC, USA.
    109Ufa Federal Research Centre of the Russian Academy of Sciences, Institute of Biochemistry and Genetics, Ufa, Russia.
    110Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
    111Sungkyunkwan University School of Medicine, Department of Obstetrics and Gynecology, Samsung Medical Center, Seoul, Korea.
    112Danish Cancer Society Research Center, Department of Virus, Lifestyle and Genes, Copenhagen, Denmark.
    113City of Hope Clinical Cancer Genetics Community Research Network, Duarte, CA, USA.
    114Maria Sklodowska-Curie National Research Institute of Oncology, Department of Pathology and Laboratory Diagnostics, Warsaw, Poland.
    115Stanford University School of Medicine, Department of Epidemiology & Population Health, Stanford, CA, USA.
    116Cancer Genetics Centre, Hong Kong Hereditary Breast Cancer Family Registry, Happy Valley, Hong Kong.
    117VIB Center for Cancer Biology, Leuven, Belgium.
    118Mayo Clinic, Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Rochester, MN, USA.
    119ONCOBELL-IDIBELL-IGTP, Catalan Institute of Oncology, CIBERONC, Hereditary Cancer Program, Barcelona, Spain.
    120BC Cancer, Cancer Control Research, Vancouver, BC, Canada.
    121University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge, UK.
    122University of California at Los Angeles, David Geffen School of Medicine, Department of Obstetrics and Gynecology, Los Angeles, CA, USA.
    123Institut Curie, Paris, France.
    124Memorial Sloan Kettering Cancer Center, Gynecology Service, Department of Surgery, New York, NY, USA.
    125Tianjin Medical University Cancer Institute and Hospital, Department of Epidemiology, Tianjin, China.
    126Genome Institute of Singapore, Human Genetics Division, Singapore, Singapore.
    127National Cancer Institute, Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA.
    128University of Texas MD Anderson Cancer Center, Department of Gynecologic Oncology and Clinical Cancer Genetics Program, Houston, TX, USA.
    129Pomeranian Medical University, Department of Genetics and Pathology, Szczecin, Poland.
    130Magee-Womens Hospital, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
    131Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Unit of Medical Genetics, Department of Medical Oncology and Hematology, Milan, Italy.
    132Duke University Hospital, Department of Surgery, Durham, NC, USA.
    133University of Hawaii Cancer Center, Cancer Epidemiology Program, Honolulu, HI, USA.
    134Aichi Cancer Center Research Institute, Division of Cancer Epidemiology and Prevention, Nagoya, Japan.
    135Princess Margaret Hospital, Division of Gynecologic Oncology, University Health Network, Toronto, ON, Canada.
    136University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge, UK.
    137Samuel Lunenfeld Research Institute, Public Health Ontario, Toronto, ON, Canada.
    138Imperial College London, Division of Cancer and Ovarian Cancer Action Research Centre, Department Surgery & Cancer, London, UK.
    139Institut Curie, Paris, France.
    140University College London, MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, London, UK.
    141Roswell Park Cancer Institute, NRG Oncology, Statistics and Data Management Center, Buffalo, NY, USA.
    142Cancer Council Victoria, Cancer Epidemiology Division, Melbourne, VIC, Australia.
    143Roswell Park Cancer Institute, Division of Cancer Prevention and Control, Buffalo, NY, USA.
    144Magee-Womens Research Institute and Hillman Cancer Center, Womens Cancer Research Center, Pittsburgh, PA, USA.
    145Veneto Institute of Oncology IOV-IRCCS, Immunology and Molecular Oncology Unit, Padua, Italy.
    146Roswell Park Cancer Institute, Division of Cancer Prevention and Control, Buffalo, NY, USA.
    147Oregon Health & Science University, Department of Obstetrics and Gynecology, Portland, OR, USA.
    148University of Pennsylvania, Basser Center for BRCA, Abramson Cancer Center, Philadelphia, PA, USA.
    149Beckman Research Institute of City of Hope, Department of Population Sciences, Duarte, CA, USA.
    150University of Helsinki, Department of Obstetrics and Gynecology, Helsinki University Hospital, Helsinki, Finland.
    151National Cancer Centre, Cancer Genetics Service, Singapore, Singapore.
    152Odense University Hospital, Department of Clinical Genetics, Odence C, Denmark.
    153Rigshospitalet, Copenhagen University Hospital, Department of Clinical Genetics, Copenhagen, Denmark.
    154Latvian Biomedical Research and Study Centre, Riga, Latvia.
    155Roswell Park Cancer Institute, Department of Gynecologic Oncology, Buffalo, NY, USA.
    156Memorial Sloan Kettering Cancer Center, Clinical Genetics Research Lab, Department of Cancer Biology and Genetics, New York, NY, USA.
    157National Institute of Oncology, Department of Molecular Genetics, Budapest, Hungary.
    158University Hospitals Leuven, Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, Leuven, Belgium.
    159The University of Chicago, Center for Clinical Cancer Genetics, Chicago, IL, USA.
    160Memorial Sloan-Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY, USA.
    161Lund University, Department of Cancer Epidemiology, Clinical Sciences, Lund, Sweden.
    162Spanish National Cancer Research Centre (CNIO), Human Cancer Genetics Programme, Madrid, Spain.
    163University of Florence, Department of Experimental and Clinical Biomedical Sciences 'Mario Serio', Medical Genetics Unit, Florence, Italy.
    164Seoul National University College of Medicine, Department of Preventive Medicine, Seoul, Korea.
    165QIMR Berghofer Medical Research Institute, Department of Genetics and Computational Biology, Brisbane, QLD, Australia.
    166University of Kansas Medical Center, Department of Pathology and Laboratory Medicine, Kansas City, KS, USA.
    167Aalborg University Hospital, Molecular Diagnostics, Aalborg, Denmark.
    168Portuguese Oncology Institute, Department of Genetics, Porto, Portugal.
    169Oregon Health & Science University, Department of Obstetrics and Gynecology, Portland, OR, USA.
    170CIBERONC, Hospital Clinico San Carlos, IdISSC (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos), Molecular Oncology Laboratory, Madrid, Spain.
    171Moffitt Cancer Center, Department of Cancer Epidemiology, Tampa, FL, USA.
    172Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
    173IFOM-the FIRC Institute of Molecular Oncology, Genome Diagnostics Program, Milan, Italy.
    174Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
    175Bashkir State University, Department of Genetics and Fundamental Medicine, Ufa, Russia.
    176Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Research, Milan, Italy.
    177Karolinska Institutet, Clinical Genetics, Stockholm, Sweden.
    178Duke University Hospital, Department of Gynecologic Oncology, Durham, NC, USA.
    179Yale School of Public Health, Chronic Disease Epidemiology, New Haven, CT, USA.
    180Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain.
    181Fox Chase Cancer Center, Population Studies Facility, Philadelphia, PA, USA.
    182Fred Hutchinson Cancer Research Center, Program in Epidemiology, Division of Public Health Sciences, Seattle, WA, USA.
    183Jena University Hospital-Friedrich Schiller University, Department of Gynaecology, Jena, Germany.
    184National Institute of Environmental Health Sciences, NIH, Epidemiology Branch, Research Triangle Park, NC, USA.
    185Centro de Investigación en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
    186Centre Hospitalier Universitaire de Québec - Université Laval Research Center, Genomics Center, Québec City, QC, Canada.
    187Faculty of Medicine and University Hospital Cologne, University of Cologne, Center for Familial Breast and Ovarian Cancer, Cologne, Germany.
    188University of Southern California, Department of Preventive Medicine, Keck School of Medicine, Los Angeles, CA, USA.
    189Hebei Medical University, Fourth Hospital, Department of Obstetrics and Gynaecology, Shijiazhuang, China.
    190Icahn School of Medicine at Mount Sinai, Department of Population Health Science and Policy, New York, NY, USA.
    191Centre Hospitalier Universitaire de Québec-Université Laval Research Center, Genomic Center, Québec City, QC, Canada.
    192Medical University of Vienna, Dept of OB/GYN and Comprehensive Cancer Center, Vienna, Austria.
    193N.N. Petrov Institute of Oncology, St. Petersburg, Russia.
    194University of Cambridge, Department of Public Health and Primary Care, Cambridge, UK.
    195Cancer Council Victoria, Cancer Epidemiology Division, Melbourne, VIC, Australia.
    196Royal Alexandra Hospital, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Edmonton, AB, Canada.
    197INSERM U830, Department of Tumour Biology, Paris, France.
    198University of South Florida, Epidemiology Center, College of Medicine, Tampa, FL, USA.
    199The Institute of Cancer Research, Division of Genetics and Epidemiology, London, UK.
    200Medical University of Vienna, Dept of OB/GYN and Comprehensive Cancer Center, Vienna, Austria.
    201Portuguese Oncology Institute, Department of Genetics, Porto, Portugal.
    202Cancer Research Malaysia, Breast Cancer Research Programme, Subang Jaya, Selangor, Malaysia.
    203Harvard T.H. Chan School of Public Health, Department of Epidemiology, Boston, MA, USA.
    204Columbia University, Department of Epidemiology, Mailman School of Public Health, New York, NY, USA.
    205Odense University Hospital, Department of Clinical Genetics, Odence C, Denmark.
    206Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, Cancer Prevention and Genetics Program, Los Angeles, CA, USA.
    207Haukeland University Hospital, Department of Obstetrics and Gynecology, Bergen, Norway.
    208Magee-Womens Hospital, University of Pittsburgh School of Medicine, Department of Medicine, Pittsburgh, PA, USA.
    209McGill University, Program in Cancer Genetics, Departments of Human Genetics and Oncology, Montréal, QC, Canada.
    210Dartmouth College, Geisel School of Medicine, Hanover, NH, USA.
    211The Ohio State University, Department of Cancer Biology and Genetics, Columbus, OH, USA.
    212German Cancer Research Center (DKFZ), Molecular Genetics of Breast Cancer, Heidelberg, Germany.
    213National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA.
    214University of Oxford, Cancer Epidemiology Unit, Oxford, UK.
    215Beth Israel Deaconess Medical Center, Department of Medical Oncology, Boston, MA, USA.
    216Harvard T.H. Chan School of Public Health, Department of Epidemiology, Boston, MA, USA.
    217Haukeland University Hospital, Department of Obstetrics and Gynecology, Bergen, Norway.
    218Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
    219University Medical Center Groningen, University Groningen, Department of Genetics, Groningen, The Netherlands.
    220University Hospitals Leuven, Division of Gynecologic Oncology, Department of Obstetrics and Gynaecology and Leuven Cancer Institute, Leuven, Belgium.
    221University of Pretoria, Department of Genetics, Arcadia, South Africa.
    222Centro de Investigación en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
    223Vanderbilt University Medical Center, Division of Quantitative Sciences, Department of Obstetrics and Gynecology, Department of Biomedical Sciences, Women's Health Research, Nashville, TN, USA.
    224Mayo Clinic, Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Rochester, MN, USA.
    225Duke Cancer Institute, Cancer Control and Population Sciences, Durham, NC, USA.
    226Faculty of Medicine and University Hospital Cologne, University of Cologne, Center for Familial Breast and Ovarian Cancer, Cologne, Germany.
    227QIMR Berghofer Medical Research Institute, Population Health Department, Brisbane, QLD, Australia.
    228National Institute of Environmental Health Sciences, NIH, Biostatistics and Computational Biology Branch, Research Triangle Park, NC, USA.
    229City of Hope, Clinical Cancer Genomics, Duarte, CA, USA.
    230National Cancer Institute, Division of Cancer Epidemiology and Genetics, Bethesda, MD, USA.
    231University of Washington, Department of Epidemiology, Seattle, WA, USA.
    232Stanford University School of Medicine, Department of Epidemiology & Population Health, Stanford, CA, USA.
    233Mayo Clinic, Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Rochester, MN, USA.
    234Karolinska Institutet, Institute of Environmental Medicine, Stockholm, Sweden.
    235University of Malaya, Department of Obstetrics and Gynaecology, University of Malaya Medical Centre, Kuala Lumpur, Malaysia.
    236University of Southern California, Department of Preventive Medicine, Keck School of Medicine, Los Angeles, CA, USA.
    237Hebei Medical University, Fourth Hospital, Department of Molecular Biology, Shijiazhuang, China.
    238National Centre for Scientific Research 'Demokritos', Molecular Diagnostics Laboratory, INRASTES, Athens, Greece.
    239University Hospital, SOD Genetica Molecolare, Pisa, Italy.
    240Vanderbilt University School of Medicine, Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
    241University of California Irvine, Department of Epidemiology, Genetic Epidemiology Research Institute, Irvine, CA, USA.
    242Magee-Womens Hospital, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
    243Institute of Biochemistry and Experimental Oncology, First Faculty od Medicine, Charles University, Prague, Czech Republic.
    244University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge, UK.
    245Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
    246The University of Sydney, Centre for Cancer Research, The Westmead Institute for Medical Research, Sydney, NSW, Australia.
    247Royal Pass Road, Tampa, FL, USA.
    248University of NSW Sydney, School of Women's and Children's Health, Faculty of Medicine, Sydney, NSW, Australia.
    249University of Michigan School of Public Health, Department of Epidemiology, Ann Arbor, MI, USA.
    250Moffitt Cancer Center, Department of Cancer Epidemiology, Tampa, FL, USA.
    251Mayo Clinic, Department of Health Science Research, Division of Epidemiology, Rochester, MN, USA.
    252Mayo Clinic, Department of Health Science Research, Division of Epidemiology, Rochester, MN, USA.
    253Emory University, Department of Epidemiology, Rollins School of Public Health, Atlanta, GA, USA.
    254Duke University Hospital, Department of Gynecologic Oncology, Durham, NC, USA.
    255QIMR Berghofer Medical Research Institute, Department of Genetics and Computational Biology, Brisbane, QLD, Australia.
    256Center for Bioinformatics and Functional Genomics, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
    257University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge, UK.
    258University of Cambridge, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, Cambridge, UK. pp10001@medschl.cam.ac.uk.
    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.


    © 2021. The Author(s).

    Publikations ID: 35027648
    Quelle: öffnen
     
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