Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants
Daniel R. Barnes(University of Cambridge), Matti A. Rookus(The Netherlands Cancer Institute), Lesley McGuffog(University of Cambridge), Goska Leslie(University of Cambridge), Thea M. Mooij(The Netherlands Cancer Institute), Joe Dennis(University of Cambridge), Nasim Mavaddat(University of Cambridge), Julian Adlard(Chapel Allerton Hospital), Munaza Ahmed(Great Ormond Street Hospital), Kristiina Aittomäki(University of Helsinki), Nadine Andrieu(Inserm), Irene L. Andrulis(Mount Sinai Hospital), Norbert Arnold(Christian-Albrechts-Universität zu Kiel), Banu Arun(The University of Texas MD Anderson Cancer Center), Jacopo Azzollini(Fondazione IRCCS Istituto Nazionale dei Tumori), Judith Balmañà(Vall d'Hebron Hospital Universitari), Rósa B. Barkardóttir(Reykjavík University), Daniel Barrowdale(University of Cambridge), Javier Benı́tez(Spanish National Cancer Research Centre), Pascaline Berthet(Centre François Baclesse), Katarzyna Białkowska(Pomeranian Medical University), Amie Blanco(University of California, San Francisco), Marinus J. Blok(Maastricht University), Bernardo Bonanni(European Institute of Oncology), Susanne E. Boonen(Zealand University Hospital), Åke Borg(Lund University), Anikó Bozsik(National Institute of Oncology), Angela R. Bradbury(University of Pennsylvania), Paul Brennan(Centre for Life), Carole Brewer(Royal Devon and Exeter Hospital), Joan Brunet(Institut d'Investigació Biomédica de Bellvitge), Saundra S. Buys(Huntsman Cancer Institute), Trinidad Caldés(Instituto de Investigación Sanitaria del Hospital Clínico San Carlos), Maria A. Caligo, Ian Campbell(The University of Melbourne), Lise Lotte Christensen(Aarhus University Hospital), Wendy K. Chung(Columbia University), Kathleen Claes(Ghent University Hospital), Chrystelle Colas(Institut Curie), Pascaline Berthet(Centre François Baclesse), Chrystelle Colas(Institut Curie), Marie‐Agnès Collonge‐Rame(Centre Hospitalier Universitaire de Besançon), Capucine Delnatte(Laboratoire de Génétique Cellulaire), Laurence Faivre(Centre Georges François Leclerc), Sophie Giraud(Hospices Civils de Lyon), Christine Lasset(Centre National de la Recherche Scientifique), Véronique Mari(Centre Antoine Lacassagne), Noura Mebirouk(Inserm), Emmanuelle Mouret‐Fourme(Institut Curie), Hélène Schuster(Inserm), Dominique Stoppa‐Lyonnet(Délégation Paris 5), Julian Adlard(Chapel Allerton Hospital), Munaza Ahmed(Great Ormond Street Hospital), Antonis C. Antoniou(University of Cambridge), Daniel Barrowdale(University of Cambridge), Paul Brennan(Centre for Life), Carole Brewer(Royal Devon and Exeter Hospital), Jackie Cook(Sheffield Children's Hospital), Rosemarie Davidson(Queen Elizabeth University Hospital), Douglas F. Easton(University of Cambridge), Rosalind A. Eeles(Royal Marsden NHS Foundation Trust), D. Gareth Evans(Manchester Academic Health Science Centre), Debra Frost(University of Cambridge), Helen Hanson(Centre Georges François Leclerc), Louise Izatt(Guy's and St Thomas' NHS Foundation Trust), Kai-Ren Ong(Birmingham Women's Hospital), Lucy Side(Princess Anne Hospital), Aoife O’Shaughnessy-Kirwan(Cambridge University Hospitals NHS Foundation Trust), Marc Tischkowitz(University of Cambridge), Lisa Walker(Oxford University Hospitals NHS Trust), Marie‐Agnès Collonge‐Rame(Centre Hospitalier Universitaire de Besançon), Jackie Cook(Sheffield Children's Hospital), Mary B. Daly(Fox Chase Cancer Center), Rosemarie Davidson(Queen Elizabeth University Hospital), Miguel de la Hoya(Instituto de Investigación Sanitaria del Hospital Clínico San Carlos), Robin De Putter(Ghent University Hospital), Capucine Delnatte(Laboratoire de Génétique Cellulaire), Peter Devilee(Leiden University Medical Center), Orland Dı́ez(Vall d'Hebron Institute of Oncology), Yuan Chun Ding(City of Hope), Susan M. Domchek(University of Pennsylvania), Cecilia M. Dorfling(University of Pretoria), Martine Dumont(Centre hospitalier universitaire de Québec), Rosalind A. Eeles(Royal Marsden NHS Foundation Trust), Bent Ejlertsen(Copenhagen University Hospital), Christoph Engel(Leipzig University), D. Gareth Evans(Manchester Academic Health Science Centre), Laurence Faivre(Centre Georges François Leclerc), Lenka Foretová(Masaryk Memorial Cancer Institute), Florentia Fostira(National Centre of Scientific Research "Demokritos"), Michael Friedländer(Cooperative Trials Group for Neuro-Oncology), Eitan Friedman(Tel Aviv University), Debra Frost(University of Cambridge), Patricia A. Ganz(UCLA Jonsson Comprehensive Cancer Center), Judy E. Garber(Dana-Farber Cancer Institute), Andrea Gehrig(University of Würzburg), Anne‐Marie Gerdes(Copenhagen University Hospital), Paul Gesta(Centre Hospitalier de Niort), Sophie Giraud(Hospices Civils de Lyon), Gord Glendon(Mount Sinai Hospital), Andrew K. Godwin(University of Kansas Medical Center), David E. Goldgar(University of Utah), Anna González‐Neira(Spanish National Cancer Research Centre), Mark H. Greene(National Cancer Institute), Daphne Gschwantler‐Kaulich(Medical University of Vienna), Eric Hahnen(University of Cologne), Ute Hamann(German Cancer Research Center), Helen Hanson, Julia Hentschel(University Hospital Leipzig), Frans B.L. Hogervorst(The Netherlands Cancer Institute), Maartje J. Hooning(Erasmus MC Cancer Institute), Judit Horváth(University of Münster), Chunling Hu(Mayo Clinic in Arizona), Peter J. Hulick(NorthShore University HealthSystem), Evgeny N. Imyanitov(Institute of Oncology NN Petrov), Georgia Chenevix‐Trench(QIMR Berghofer Medical Research Institute), Kelly‐Anne Phillips(The University of Melbourne), Amanda B. Spurdle(QIMR Berghofer Medical Research Institute), Marinus J. Blok(Maastricht University), Peter Devilee(Leiden University Medical Center), Frans B.L. Hogervorst(The Netherlands Cancer Institute), Maartje J. Hooning(Erasmus MC Cancer Institute), Marco J. Koudijs(University Medical Center Utrecht), Arjen R. Mensenkamp(Radboud University Nijmegen), Hanne Meijers‐Heijboer(Amsterdam University Medical Centers), Matti A. Rookus(The Netherlands Cancer Institute), Klaartje van Engelen(Amsterdam University Medical Centers), Nadine Andrieu(Inserm), Catherine Noguès(Inserm), Claudine Isaacs(Georgetown University), Louise Izatt(Guy's and St Thomas' NHS Foundation Trust), Á. Izquierdo(Institut d'Investigació Biomédica de Bellvitge), Anna Jakubowska(Pomeranian Medical University), Paul A. James(The University of Melbourne), Ramunas Janavicius(Vilnius University), Esther M. John(Stanford University), Joseph Vijai(Memorial Sloan Kettering Cancer Center), Beth Y. Karlan(Cedars-Sinai Medical Center), Karin Kast(University Hospital Carl Gustav Carus), Marco J. Koudijs(University Medical Center Utrecht), Torben A. Kruse(Odense University Hospital), Ava Kwong(Hong Kong Sanatorium and Hospital), Yael Laitman(Sheba Medical Center), Christine Lasset(Centre National de la Recherche Scientifique), Conxi Lázaro(Institut d'Investigació Biomédica de Bellvitge), Jenny Lester(Cedars-Sinai Medical Center), Fabienne Lesueur(Inserm), Annelie Liljegren(Karolinska Institutet), Jennifer T. Loud(National Cancer Institute), Jan Lubiński(Pomeranian Medical University), Phuong L. Mai(University of Pittsburgh), Siranoush Manoukian(Fondazione IRCCS Istituto Nazionale dei Tumori), Véronique Mari(Centre Antoine Lacassagne), Noura Mebirouk(Inserm), Hanne Meijers‐Heijboer(Amsterdam University Medical Centers), Alfons Meindl(Ludwig-Maximilians-Universität München), Arjen R. Mensenkamp(Radboud University Nijmegen), Austin Miller(Roswell Park Comprehensive Cancer Center), Marco Montagna(Istituto Oncologico Veneto), Emmanuelle Mouret‐Fourme(Institut Curie), Semanti Mukherjee(Memorial Sloan Kettering Cancer Center), Anna Marie Mulligan(University Health Network), Katherine L. Nathanson(University of Pennsylvania), Susan L. Neuhausen(City of Hope), Heli Nevanlinna(University of Helsinki), Dieter Niederacher(Düsseldorf University Hospital), Finn Cilius Nielsen(Copenhagen University Hospital), Liene Ņikitina-Zaķe(Latvian Biomedical Research and Study Centre), Catherine Noguès(Inserm), Edith Olah(National Institute of Oncology), Olufunmilayo I. Olopade(University of Chicago), Kai-Ren Ong(Birmingham Women's Hospital), Aoife O’Shaughnessy-Kirwan(Cambridge University Hospitals NHS Foundation Trust), Ana Osório(Spanish National Cancer Research Centre), Claus‐Eric Ott(Charité - Universitätsmedizin Berlin), Laura Papi(University of Florence), Sue K. Park(Seoul National University), Michael T. Parsons(QIMR Berghofer Medical Research Institute), Inge Søkilde Pedersen(Aalborg University Hospital), Bernard Peissel(Fondazione IRCCS Istituto Nazionale dei Tumori), Ana Peixoto(Instituto Português de Oncologia Francisco Gentil), Paolo Peterlongo(IFOM), Georg Pfeiler(Comprehensive Cancer Center Vienna), Kelly‐Anne Phillips(The University of Melbourne), Karolina Prajzendanc(Pomeranian Medical University), Miguel Ángel Pujana(Institut d'Investigació Biomédica de Bellvitge), Paolo Radice(Fondazione IRCCS Istituto Nazionale dei Tumori), Juliane Ramser(TUM Klinikum), Susan J. Ramus(Garvan Institute of Medical Research), Johanna Rantala(Karolinska Institutet), Gad Rennert(Carmel Medical Center), Harvey A. Risch(Yale University), Mark E. Robson(Memorial Sloan Kettering Cancer Center), Karina Rønlund(Vejle Sygehus), Ritu Salani(The Ohio State University Wexner Medical Center), Hélène Schuster(Inserm), Leigha Senter(Cancer Genetics (United States)), Payal D. Shah(University of Pennsylvania), Priyanka Sharma(University of Kansas Medical Center), Lucy Side(Princess Anne Hospital), Christian F. Singer(Comprehensive Cancer Center Vienna), Thomas P. Slavin(City of Hope), Penny Soucy(Centre hospitalier universitaire de Québec), Melissa C. Southey(The University of Melbourne), Amanda B. Spurdle(QIMR Berghofer Medical Research Institute), Doris Steinemann(Medizinische Hochschule Hannover), Zoe Steinsnyder(Memorial Sloan Kettering Cancer Center), Dominique Stoppa‐Lyonnet(Délégation Paris 5), Christian Sutter(Heidelberg University), Yen Y. Tan(Medical University of Vienna), Manuel R. Teixeira(Universidade do Porto), Soo‐Hwang Teo(University of Malaya), Darcy L. Thull(University of Pittsburgh), Marc Tischkowitz(University of Cambridge), Silvia Tognazzo(Istituto Oncologico Veneto), Amanda E. Toland(The Ohio State University), Alison H. Trainer(The University of Melbourne), Nadine Tung(Beth Israel Deaconess Medical Center), Klaartje van Engelen(Amsterdam University Medical Centers), Elizabeth J. van Rensburg(University of Pretoria), Ana Vega(Complejo Hospitalario Universitario de Santiago), Jeroen Vierstraete(Ghent University Hospital), Gabriel Wagner(Comprehensive Cancer Center Vienna), Lisa Walker(Oxford University Hospitals NHS Trust), Shan Wang‐Gohrke(University Hospital Ulm), Barbara Wappenschmidt(University of Cologne), Jeffrey N. Weitzel(City of Hope), Siddhartha Yadav(Mayo Clinic in Arizona), Xin Yang(University of Cambridge), Drakoulis Yannoukakos(National Centre of Scientific Research "Demokritos"), Dario Zimbalatti(Fondazione IRCCS Istituto Nazionale dei Tumori), Kenneth Offit(Memorial Sloan Kettering Cancer Center), Mads Thomassen(Odense University Hospital), Fergus J. Couch(Mayo Clinic in Arizona), Rita K. Schmutzler(University of Cologne), Jacques Simard(Centre hospitalier universitaire de Québec), Douglas F. Easton(University of Cambridge), Georgia Chenevix‐Trench(QIMR Berghofer Medical Research Institute), Antonis C. Antoniou(University of Cambridge)
Cited by 145Open Access
Abstract
PURPOSE: We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers. METHODS: Retrospective cohort data on 18,935 BRCA1 and 12,339 BRCA2 female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. RESULTS: ) carriers. The associations in the prospective cohort were similar. CONCLUSION: Population-based PRS are strongly associated with BC and EOC risks for BRCA1/2 carriers and predict substantial absolute risk differences for women at PRS distribution extremes.
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