The predictive ability of the 313 variant–based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant

Inge Lakeman; Alexandra van den Broek; Juliën Vos; Daniel Barnes; Julian Adlard; Irene Andrulis; Adalgeir Arason; Norbert Arnold; Banu Arun; Judith Balmaña; Daniel Barrowdale; Javier Benitez; Ake Borg; Trinidad Caldés; Maria Caligo; Wendy Chung; Kathleen Claes; J Margriet Collée; Fergus Couch; Mary Daly; Joe Dennis; Mallika Dhawan; Susan Domchek; Ros Eeles; Christoph Engel; D Gareth Evans; Lidia Feliubadaló; Lenka Foretova; Eitan Friedman; Debra Frost; Patricia Ganz; Judy Garber; Simon Gayther; Anne-Marie Gerdes; Andrew Godwin; David Goldgar; Eric Hahnen; Christopher Hake; Ute Hamann; Frans Hogervorst; Maartje Hooning; John Hopper; Peter Hulick; Evgeny Imyanitov; Claudine Isaacs; Louise Izatt; Anna Jakubowska; Paul James; Ramunas Janavicius; Uffe Birk Jensen; Yue Jiao; Esther John; Vijai Joseph; Beth Karlan; Carolien Kets; Irene Konstantopoulou; Ava Kwong; Clémentine Legrand; Goska Leslie; Fabienne Lesueur; Jennifer Loud; Jan Lubiński; Siranoush Manoukian; Lesley Mcguffog; Austin Miller; Denise Molina Gomes; Marco Montagna; Emmanuelle Mouret-Fourme; Katherine Nathanson; Susan Neuhausen; Heli Nevanlinna; Joanne Ngeow Yuen Yie; Edith Olah; Olufunmilayo Olopade; Sue Park; Michael Parsons; Paolo Peterlongo; Marion Piedmonte; Paolo Radice; Johanna Rantala; Gad Rennert; Harvey Risch; Rita Schmutzler; Priyanka Sharma; Jacques Simard; Christian Singer; Zsofia Stadler; Dominique Stoppa-Lyonnet; Christian Sutter; Yen Yen Tan; Manuel Teixeira; Soo Hwang Teo; Alex Teulé; Mads Thomassen; Darcy Thull; Marc Tischkowitz; Amanda Toland; Nadine Tung; Elizabeth van Rensburg; Ana Vega; Barbara Wappenschmidt; Peter Devilee; Christi van Asperen; Jonine Bernstein; Kenneth Offit; Douglas Easton; Matti Rookus; Georgia Chenevix-Trench; Antonis Antoniou; Mark Robson; Marjanka Schmidt; Kathleen B.M. Claes; Emmanuelle Barouk-Simonet; Muriel Belotti; Pascaline Berthet; Yves-Jean Bignon; Valérie Bonadona; Brigitte Bressac-de Paillerets; Bruno Buecher; Sandrine Caputo; Olivier Caron; Laurent Castera; Virginie Caux-Moncoutier; Chrystelle Colas; Marie-Agnès Collonge-Rame; Isabelle Coupier; Antoine de Pauw; Capucine Delnatte; Camille Elan; Laurence Faivre; Sandra Fert Ferrer; Marion Gauthier-Villars; Paul Gesta; Sophie Giraud; Lisa Golmard; Claude Houdayer; Christine Lasset; Maïté Laurent; Dominique Leroux; Michel Longy; Véronique Mari; Sylvie Mazoyer; Noura Mebirouk; Isabelle Mortemousque; Fabienne Prieur; Pascal Pujol; Claire Saule; Helene Schuster; Nicolas Sevenet; Hagay Sobol; Johanna Sokolowska; Laurence Venat-Bouvet; Munaza Ahmed; Julian Barwell; Angela Brady; Paul Brennan; Carole Brewer; Jackie Cook; Rosemarie Davidson; Alan Donaldson; Alison Dunning; Jacqueline Eason; Diana Eccles; Helen Gregory; Helen Hanson; Patricia Harrington; Alex Henderson; Shirley Hodgson; M. John Kennedy; Fiona Lalloo; Clare Miller; Patrick Morrison; Kai-Ren Ong; Aoife O’shaughnessy-Kirwan; Jo Perkins; Mary Porteous; Mark Rogers; Lucy Side; Katie Snape; Lisa Walker; Gord Glendon; Anna Marie Mulligan; Cora Aalfs; Muriel Adank; Margreet G.E.M. Ausems; Marinus Blok; Encarna Gómez Garcia; Bernadette A.M. Heemskerk-Gerritsen; Antoinette Hollestelle; Agnes Jager; Linetta Koppert; Marco Koudijs; Mieke Kriege; Hanne E.J. Meijers-Heijboer; Arjen Mensenkamp; Thea Mooij; Jan Oosterwijk; Ans M.W. van den Ouweland; Frederieke van Der Baan; Annemieke van Der Hout; Lizet van Der Kolk; Rob van Der Luijt; Carolien H.M. van Deurzen; Helena van Doorn; Klaartje van Engelen; Liselotte van Hest; Theo A.M. van Os; Senno Verhoef; Maartje Vogel; Juul Wijnen; Jonathan Beesley; Stephen Fox; Helene Holland; Kelly-Anne Phillips; Amanda Spurdle

doi:10.1038/s41436-021-01198-7

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The predictive ability of the 313 variant–based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant

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The predictive ability of the 313 variant–based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant

Inge Lakeman, Alexandra van den Broek, Juliën Vos, Daniel Barnes, Julian Adlard, Irene Andrulis, Adalgeir Arason, Norbert Arnold, Banu Arun, Judith Balmaña, …

Genetics in Medicine, Vol.23(9), pp.1726-1737

09/2021

DOI: https://doi.org/10.1038/s41436-021-01198-7

PMCID: PMC8460445

PMID: 34113011

Abstract

Adult

BRCA1 Protein

Risk Factors

BRCA2 Protein

Breast Neoplasms

Female

Genetic Predisposition to Disease

Heterozygote

Humans

Mutation

Retrospective Studies

Purpose: To evaluate the association between a previously published 313 variant-based breast cancer (BC) polygenic risk score (PRS313) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes.Methods: We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS313 and CBC risk.Results: For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS313 showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06-1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS313, HR = 1.15, 95% CI (1.07-1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC < age 40 years, the cumulative PRS313 5th and 95th percentile 10-year CBC risks were 22% and 32% for BRCA1 and 13% and 23% for BRCA2 heterozygotes, respectively.Conclusion: The PRS313 can be used to refine individual CBC risks for BRCA1/2 heterozygotes of European ancestry, however the PRS313 needs to be considered in the context of a multifactorial risk model to evaluate whether it might influence clinical decision-making.

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Title: The predictive ability of the 313 variant–based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant
Creators - without role: Inge Lakeman
Alexandra van den Broek - The Netherlands Cancer Institute
Juliën Vos
Daniel Barnes - University of Cambridge
Julian Adlard - Chapel Allerton Hospital
Irene Andrulis - Mount Sinai Hospital
Adalgeir Arason - Reykjavík University
Norbert Arnold - Kiel University
Banu Arun - The University of Texas MD Anderson Cancer Center
Judith Balmaña - Vall d'Hebron Hospital Universitari
Daniel Barrowdale - University of Cambridge
Javier Benitez - Cancer Genetics
Ake Borg - Lund University
Trinidad Caldés - Centro de Investigación Biomédica en Red
Maria Caligo - Istituto di Genetica Molecolare
Wendy Chung - Columbia University
Kathleen Claes - Ghent University
J Margriet Collée - Erasmus MC
Fergus Couch - Mayo Clinic in Arizona
Mary Daly - Fox Chase Cancer Center
Joe Dennis - University of Cambridge
Mallika Dhawan - Cancer Genetics
Susan Domchek - University of Pennsylvania
Ros Eeles - Royal Marsden NHS Foundation Trust
Christoph Engel - Leipzig University
D Gareth Evans - University of Manchester
Lidia Feliubadaló - Institut d'Investigació Biomédica de Bellvitge
Lenka Foretova - Masaryk Memorial Cancer Institute
Eitan Friedman - Tel Aviv University
Debra Frost - University of Cambridge
Patricia Ganz - UCLA Jonsson Comprehensive Cancer Center
Judy Garber - Dana-Farber Cancer Institute
Simon Gayther - Cedars-Sinai Medical Center
Anne-Marie Gerdes
Andrew Godwin - University of Kansas Medical Center
David Goldgar - University of Utah
Eric Hahnen - University Hospital Cologne
Christopher Hake - ProHealth Care
Ute Hamann - German Cancer Research Center
Frans Hogervorst
Maartje Hooning - Erasmus MC Cancer Institute
John Hopper - University of Melbourne
Peter Hulick - NorthShore University HealthSystem
Evgeny Imyanitov - Institute of Oncology NN Petrov
Claudine Isaacs - Georgetown University
Louise Izatt - Guy's and St Thomas' NHS Foundation Trust
Anna Jakubowska - Pomeranian Medical University
Paul James - Peter MacCallum Cancer Centre
Ramunas Janavicius - Vilnius University
Uffe Birk Jensen - Aarhus University Hospital
Yue Jiao - Institut Curie
Esther John - Stanford University
Vijai Joseph
Beth Karlan - University of California, Los Angeles
Carolien Kets - The Netherlands Cancer Institute
Irene Konstantopoulou - National Centre of Scientific Research "Demokritos"
Ava Kwong - Hong Kong Sanatorium and Hospital
Clémentine Legrand - Centre Hospitalier Universitaire de Grenoble
Goska Leslie - University of Cambridge
Fabienne Lesueur - École Nationale Supérieure des Mines de Paris
Jennifer Loud - National Cancer Institute
Jan Lubiński - Pomeranian Medical University
Siranoush Manoukian - Fondazione IRCCS Istituto Nazionale dei Tumori
Lesley Mcguffog - University of Cambridge
Austin Miller - Roswell Park Comprehensive Cancer Center
Denise Molina Gomes - Centre Hospitalier Intercommunal de Poissy
Marco Montagna - Istituto Oncologico Veneto
Emmanuelle Mouret-Fourme - Institut Curie
Katherine Nathanson - University of Pennsylvania
Susan Neuhausen - City Of Hope National Medical Center
Heli Nevanlinna - University of Helsinki
Joanne Ngeow Yuen Yie
Edith Olah - National Institute of Oncology
Olufunmilayo Olopade - University of Chicago
Sue Park - Seoul National University
Michael Parsons - QIMR Berghofer Medical Research Institute
Paolo Peterlongo - IFOM
Marion Piedmonte - NRG Oncology
Paolo Radice - Fondazione IRCCS Istituto Nazionale dei Tumori
Johanna Rantala - Karolinska Institutet
Gad Rennert - Carmel Medical Center
Harvey Risch
Rita Schmutzler - University Hospital Cologne
Priyanka Sharma - University of Kansas Medical Center
Jacques Simard - Centre hospitalier universitaire de Québec
Christian Singer - Medical University of Vienna
Zsofia Stadler - Memorial Sloan Kettering Cancer Center
Dominique Stoppa-Lyonnet - Institut Curie
Christian Sutter - University Hospital Heidelberg
Yen Yen Tan - Medical University of Vienna
Manuel Teixeira - Instituto Português de Oncologia Francisco Gentil
Soo Hwang Teo
Alex Teulé - Institut d'Investigació Biomédica de Bellvitge
Mads Thomassen - Odense University Hospital
Darcy Thull - University of Pittsburgh
Marc Tischkowitz - National Institute for Health Research
Amanda Toland - The Ohio State University
Nadine Tung - Beth Israel Deaconess Medical Center
Elizabeth van Rensburg - University of Pretoria
Ana Vega - Fundación Pública Galega de Medicina Xenómica
Barbara Wappenschmidt - University Hospital Cologne
Peter Devilee - Leiden University Medical Center
Christi van Asperen - Leiden University Medical Center
Jonine Bernstein - Memorial Sloan Kettering Cancer Center
Kenneth Offit - Memorial Sloan Kettering Cancer Center
Douglas Easton - Cancer Research UK Cambridge Center
Matti Rookus - The Netherlands Cancer Institute
Georgia Chenevix-Trench - QIMR Berghofer Medical Research Institute
Antonis Antoniou - University of Cambridge
Mark Robson - Memorial Sloan Kettering Cancer Center
Marjanka Schmidt - The Netherlands Cancer Institute
Kathleen B.M. Claes
Emmanuelle Barouk-Simonet - Institut Bergonié
Muriel Belotti - Institut Curie
Pascaline Berthet - Centre François Baclesse
Yves-Jean Bignon
Valérie Bonadona - Centre Léon Bérard
Brigitte Bressac-de Paillerets
Bruno Buecher - Institut Curie
Sandrine Caputo - Institut Curie
Olivier Caron - Institut Gustave Roussy
Laurent Castera - Centre François Baclesse
Virginie Caux-Moncoutier - Institut Curie
Chrystelle Colas - Institut Curie
Marie-Agnès Collonge-Rame
Isabelle Coupier - Hôpital Arnaud de Villeneuve
Antoine de Pauw - Institut Curie
Capucine Delnatte - Institut de Cancérologie de l'Ouest
Camille Elan - Institut Curie
Laurence Faivre - Centre Hospitalier Universitaire Dijon Bourgogne
Sandra Fert Ferrer
Marion Gauthier-Villars - Institut Curie
Paul Gesta - Centre Hospitalier de Niort
Sophie Giraud - Hospices Civils de Lyon
Lisa Golmard - Institut Curie
Claude Houdayer - Inserm
Christine Lasset - Centre Léon Bérard
Maïté Laurent - Institut Curie
Dominique Leroux - Centre Hospitalier Universitaire de Grenoble
Michel Longy - Institut Bergonié
Véronique Mari - Centre Antoine Lacassagne
Sylvie Mazoyer - Centre National de la Recherche Scientifique
Noura Mebirouk - Institut Curie
Isabelle Mortemousque - Bretonneau Hospital
Fabienne Prieur - Centre Hospitalier Universitaire de Saint-Étienne
Pascal Pujol - Hôpital Arnaud de Villeneuve
Claire Saule - Institut Curie
Helene Schuster
Nicolas Sevenet - Institut Bergonié
Hagay Sobol - Institut Paoli-Calmettes
Johanna Sokolowska - Centre Hospitalier Régional et Universitaire de Nancy
Laurence Venat-Bouvet - Hôpital Dupuytren
Munaza Ahmed - University College London
Julian Barwell - University Hospitals of Leicester NHS Trust
Angela Brady - London North West Healthcare NHS Trust
Paul Brennan - KK Women's and Children's Hospital
Carole Brewer - Royal Devon and Exeter Hospital
Jackie Cook - Sheffield Children's Hospital
Rosemarie Davidson
Alan Donaldson - St Michael's Hospital
Alison Dunning - Cancer Research UK Cambridge Center
Jacqueline Eason - Nottingham University Hospitals NHS Trust
Diana Eccles - University of Southampton
Helen Gregory - NHS Grampian
Helen Hanson - St George's Hospital
Patricia Harrington - Cancer Research UK Cambridge Center
Alex Henderson - Centre for Life
Shirley Hodgson - St George's, University of London
M. John Kennedy - St. James's Hospital
Fiona Lalloo - Cornell University
Clare Miller - University of Liverpool
Patrick Morrison - University of Ulster
Kai-Ren Ong
Aoife O’shaughnessy-Kirwan - SingHealth Duke-NUS Academic Medical Centre
Jo Perkins - University of Cambridge
Mary Porteous - Western General Hospital
Mark Rogers - University Hospital of Wales
Lucy Side - Princess Anne Hospital
Katie Snape - St George's, University of London
Lisa Walker - Churchill Hospital
Gord Glendon - Lunenfeld-Tanenbaum Research Institute
Anna Marie Mulligan - University of Toronto
Cora Aalfs - Amsterdam University Medical Centers
Muriel Adank - The Netherlands Cancer Institute
Margreet G.E.M. Ausems - University Medical Center Utrecht
Marinus Blok - Maastricht University
Encarna Gómez Garcia
Bernadette A.M. Heemskerk-Gerritsen - Erasmus MC Cancer Institute
Antoinette Hollestelle - Erasmus MC Cancer Institute
Agnes Jager - Erasmus MC Cancer Institute
Linetta Koppert - Erasmus MC Cancer Institute
Marco Koudijs - University Medical Center Utrecht
Mieke Kriege - Erasmus MC Cancer Institute
Hanne E.J. Meijers-Heijboer
Arjen Mensenkamp - Radboud University Nijmegen
Thea Mooij - Oncode Institute
Jan Oosterwijk - University Medical Center Groningen
Ans M.W. van den Ouweland - Erasmus MC
Frederieke van Der Baan - Oncode Institute
Annemieke van Der Hout - University Medical Center Groningen
Lizet van Der Kolk - The Netherlands Cancer Institute
Rob van Der Luijt - University Medical Center Utrecht
Carolien H.M. van Deurzen - Erasmus MC
Helena van Doorn - Erasmus MC Cancer Institute
Klaartje van Engelen - Amsterdam UMC Location VUmc
Liselotte van Hest - Vrije Universiteit Amsterdam
Theo A.M. van Os - Amsterdam University Medical Centers
Senno Verhoef - The Netherlands Cancer Institute
Maartje Vogel - The Netherlands Cancer Institute
Juul Wijnen - Leiden University Medical Center
Jonathan Beesley - QIMR Berghofer Medical Research Institute
Stephen Fox - Peter MacCallum Cancer Centre
Helene Holland - QIMR Berghofer Medical Research Institute
Kelly-Anne Phillips
Amanda Spurdle - QIMR Berghofer Medical Research Institute
Publication Details: Genetics in Medicine, Vol.23(9), pp.1726-1737
Identifiers: 9937626909311
Academic Unit: Maladies Infectieuses et Vecteurs : Ecologie, Génétique, Evolution et Contrôle - MIVEGEC
Language: English
Resource Type: Journal article
Local Fields: hal-03652349