Journal article

Common breast cancer susceptibility alleles are associated with tumour subtypes in BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2

Anna Marie Mulligan, Fergus J Couch, Daniel Barrowdale, Susan M Domchek, Diana Eccles, Heli Nevanlinna, Susan J Ramus, Mark Robson, Mark Sherman, Amanda B Spurdle, Barbara Wappenschmidt, Andrew Lee, Lesley McGuffog, Sue Healey, Olga M Sinilnikova, Ramunas Janavicius, Thomas VO Hansen, Finn C Nielsen, Bent Ejlertsen, Ana Osorio Show all



INTRODUCTION: Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour. METHODS: We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumour, to assess the associations of 12 loci with breast cancer tumour characteristics. Associations were evaluat..

View full abstract


Awarded by NIH, NCI

Awarded by Russian Federation for Basic Research

Awarded by Federal Agency for Science and Innovations

Awarded by Commission of the European Communities

Awarded by Royal Society

Awarded by NIH

Awarded by Research Excellence (SPORE) in Breast Cancer

Awarded by Ministero della Salute

Awarded by Associazione Italiana per la Ricerca sul Cancro

Awarded by Cancer Research UK

Awarded by Tissue Culture Shared Registry at Georgetown University (NIH/NCI)

Awarded by Cancer Genetics Network

Awarded by German Cancer Aid

Awarded by Association for International Cancer

Awarded by European Community

Awarded by National Cancer Institute, National Institutes of Health



Awarded by National Institute for Health Research

Funding Acknowledgements

This work was supported by Cancer Research UK grants C12292/A11174 and C1287/A10118. The research leading to these results has received funding from the European Community's Seventh Framework Programme under grant agreement n<SUP>o</SUP> 223175 (HEALTH-F2-2009-223175). ACA is a CR-UK Senior Cancer Research Fellow, DFE is CR-UK Principal Research Fellow. Study specific acknowledgments Breast Cancer Family Registry (BCFR) This work was supported by the National Cancer Institute, National Institutes of Health under RFA-CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Columbia University (U01 CA69398), Fox Chase Cancer Center (U01 CA69631), Huntsman Cancer Institute (U01 CA69446), Cancer Prevention Institute of California (formerly the Northern California Cancer Center) (U01 CA69417), University of Melbourne (U01 CA69638), and Research Triangle Institute Informatics Support Center (RFP No. N02PC45022-46). Samples from the FCCC, HCI, and CPIC were processed and distributed by the Coriell institute for Medical Research. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the BCFR, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government or the BCFR. The Baltic Familial Breast and Ovarian Cancer Consortium (BFBOCC Latvia and Lithuania) Lithuania: This work is supported by the Research Council of Lithuania grant LIG-19/2010 to Ramunas Janavicius. Latvia: We acknowledge Genome Database of Latvian Population, Latvian Biomedical Research and Study Center for providing data and DNA samples. This work is supported by Liepaja's municipal council to Laima Tihomirova (Latvian Biomedical Research and Study Centre). Copenhagen Breast Cancer Study (CBCS)We thank the NEYE Foundation for financial support The Deutsches Krebsforschungszentrum (DKFZ) study The study was supported by the DKFZ.The study was supported by the DKFZ.The CONSIT TEAM is supported by grants from Associazione Italiana per la Ricerca sul Cancro (4017) and by funds from Italian citizens who allocated the 5 x 1,000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumouri, according to Italian laws (INT-Institutional strategic projects "5 x 1000") to PP and grants from Fondazione Italiana per la Ricerca sul Cancro (Special Project "Hereditary tumours"), Ministero della Salute (Extraordinary National Cancer Program 2006 "Alleanza contro il Cancro", and "Progetto Tumouri Femminili") and Ministero dell'Universita' e Ricerca (RBLAO3-BETH) to PR. CONSIT TEAM acknowledges the contribution of Gaia Roversi, Carla B. Ripamonti, Marilena Morganti and Marco Pierotti of the of the Fondazione IRCCS Istituto Nazionale dei Tumouri, Milan, Italy; Monica Barile of the Istituto Europeo di Oncologia, Milan, Italy and Liliana Varesco of the Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy. Epidemiological study of BRCA1 and BRCA2 mutation carriers (EMBRACE) EMBRACE Collaborating Centers are: Coordinating Centre, Cambridge: Steve Ellis, Elena Fineberg, Radka Platte. North of Scotland Regional Genetics Service, Aberdeen: Zosia Miedzybrodzka. Northern Ireland Regional Genetics Service, Belfast: Patrick Morrison, Lisa Jeffers. West Midlands Regional Clinical Genetics Service, Birmingham: Trevor Cole, Kai-ren Ong, Jonathan Hoffman. South West Regional Genetics Service, Bristol: Margaret James. East Anglian Regional Genetics Service, Cambridge: Joan Paterson, Sarah Downing, Amy Taylor. Medical Genetics Services for Wales, Cardiff: T. Rogers,. St James's Hospital, Dublin & National Centre for Medical Genetics, Dublin: M. John Kennedy, David Barton. South East of Scotland Regional Genetics Service, Edinburgh: Mary Porteous, Sarah Drummond. Peninsula Clinical Genetics Service, Exeter: Carole Brewer, Emma Kivuva, Anne Searle, Selina Goodman, Kathryn Hill. West of Scotland Regional Genetics Service, Glasgow: Victoria Murday, Nicola Bradshaw, Lesley Snadden, Mark Longmuir, Catherine Watt, Sarah Gibson, Eshika Haque, Ed Tobias, Alexis Duncan. South East Thames Regional Genetics Service, Guy's Hospital London: Chris Jacobs, Caroline Langman, Anna Whaite. North West Thames Regional Genetics Service, Harrow. Leicestershire Clinical Genetics Service, Leicester. Yorkshire Regional Genetics Service, Leeds: Carol Chu, Julie Miller. Cheshire and Merseyside Clinical Genetics Service, Liverpool: Ian Ellis. Manchester Regional Genetics Service, Manchester: Jane Taylor. North East Thames Regional Genetics Service, NE Thames, London: Alison Male, Cheryl Berlin. Nottingham Centre for Medical Genetics, Nottingham: Rebecca Collier. Northern Clinical Genetics Service, Newcastle: Fiona Douglas, Oonagh Claber, Irene Jobson. Oxford Regional Genetics Service, Oxford: Lisa Walker, Diane McLeod, Dorothy Halliday, Sarah Durell, Barbara Stayner. The Institute of Cancer Research and Royal Marsden NHS Foundation Trust: Susan Shanley, Nazneen Rahman, Richard Houlston, Elizabeth Bancroft, Lucia D'Mello, Elizabeth Page, Audrey Ardern-Jones, Kelly Kohut, Jennifer Wiggins, Elena Castro, Anita Mitra, Lisa Robertson. North Trent Clinical Genetics Service, Sheffield: Oliver Quarrell, Cathryn Bardsley. South West Thames Regional Genetics Service, London: Shirley Hodgson, Sheila Goff, Glen Brice, Lizzie Winchester, Charlotte Eddy, Vishakha Tripathi, Virginia Attard. Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton: Anneke Lucassen, Gillian Crawford, Donna McBride, Sarah Smalley.EMBRACE is supprted by Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles, Elizabeth Bancroft and Lucia D'Mello are also supported by Cancer Research UK Grant C5047/A8385. Fox Chase Cancer Center Study (FCCC)A.K.G. was funded by U01CA69631, 5U01CA113916, and the Eileen Stein Jacoby Fund. The author acknowledges support from The University of Kansas Cancer Center and the Kansas Bioscience Authority Eminent Scholar Program. A. K. G. is the Chancellors Distinguished Chair in Biomedical Sciences endowed Professor.Work is supported by the Familial Cancer Registry (CI) and the Tissue Culture Shared Registry at Georgetown University (NIH/NCI grant P30-CA051008), the Cancer Genetics Network (HHSN261200744000C) (CI), and Swing Fore the Cure (CI).The German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) GC-HBOC is supported by a grant of the German Cancer Aid (grant 109076), the Centre of Molecular Medicine Cologne (CMMC).The study was supported by the Ligue National Contre le Cancer; Association for International Cancer Research Grant (AICR-07-0454); and the Association "Le cancer du sein, parlons-en!" Award. We wish to thank all the GEMO collaborating groups for their contribution to this study. GEMO Collaborating Centers are: Coordinating Centres, Unite Mixte de Genetique Constitutionnelle des Cancers Frequents, Centre Hospitalier Universitaire de Lyon/Centre Leon Berard, et Equipe "Genetique du cancer du sein, Centre de Recherche en Cancerologie de Lyon: Laure Barjhoux, Carole Verny-Pierre, Sophie Giraud, and Service de Genetique Oncologique, Institut Curie, Parise Marion Gauthier-Villars, Bruno Buecher, Claude Houdayer, Muriel Belotti, Carole Tirapo, Antoine de Pauw. Institut Gustave Roussy, Villejuif: Brigitte Bressac-de-Paillerets, Audrey Remenieras, Veronique Byrde, Olivier Caron, Gilbert Lenoir. Centre Jean Perrin, Clermont-Ferrand: Yves-Jean Bignon, Nancy Uhrhammer. Centre Leon Berard, Lyon: Christine Lasset, Valerie Bonadona. Centre Francois Baclesse, Caen. Institut Paoli Calmettes, Marseille: Hagay Sobol, Violaine Bourdon, Tetsuro Noguchi, Francois Eisinger. Groupe Hospitalier Pitie-Salpetriere, Paris: Florence Coulet, Chrystelle Colas, Florent Soubrier. CHU de Arnaud-de-Villeneuve, Montpellier. Centre Oscar Lambret, Lille: Jean-Philippe Peyrat, Joelle Fournier, Francoise Revillion, Philippe Vennin, Claude Adenis. Hopital Rene Huguenin/Institut Curie, St Cloud: Etienne Rouleau, Rosette Lidereau, Liliane Demange, Catherine Nogues. Centre Paul Strauss, Strasbourg. Institut Bergonie, Bordeaux: Emmanuelle Barouk-Simonet, Francoise Bonnet, Virginie Bubien. Institut Claudius Regaud, Toulouse: Christine Toulas, Rosine Guimbaud, Laurence Gladieff, Viviane Feillel. CHU de Grenoble: Dominique Leroux, Helene Dreyfus, Christine Rebischung, Magalie Peysselon. CHU de Dijon: Fanny Coron, Laurence Faivre. CHU de St-Etienne: Fabienne Prieur. Hetel Dieu Centre Hospitalier, Chambery: Sandra Fert Ferrer. Centre Antoine Lacassagne, Nice: Marc Frenay. CHU de Limoges: Laurence Venat-Bouvet. CHU de Nantes: Capucine Delnatte. CHU Bretonneau, Tours. Creighton University, Omaha, USA: Henry T. Lynch, Carrie L. Snyder.The ILUH group was supported by the Icelandic Association "Walking for Breast Cancer Research" and by the Landspitali University Hospital Research Fund.This study was supported by "Ministero della Salute" ("Progetto Tumouri Femminili and grant numbers RFPS 2006-5-341353, ACC2/R6.9") Kathleen Cuningham Consortium for Research into Familial Breast Cancer (kConFab)The MAYO study was supported by NIH grants CA116167, CA128978, a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), and awards from the Komen Foundation for the Cure and the Breast Cancer Research Foundation.The study is supported by grant from the Breast Cancer Research Foundation, Starr Cancer Consortium, Norman and Carol Stone Genetic Research Fund, The Robert and Kate Niehaus Clinical Genetics Initiative at MSKCCThe research of Drs. PL Mai and MH Greene was supported by the Intramural Research Program of the US National Cancer Institute, and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc., Rockville, MD.This work has been supported by the Russian Federation for Basic Research (grants 10-04-92601, 10-04-92110, 11-04-00227), the Federal Agency for Science and Innovations (contract 02.740.11.0780), the Commission of the European Communities (grant PITN-GA-2009-238132) and through a Royal Society International Joint grant (JP090615).The study received funding from the NIH, NCI Bay Area Breast Cancer SPORE (P50 CA 058207) and the Avon Foundation. We acknowledge support from the UCSF Helen Diller Family Comprehensive Cancer Center UK and Gilda Radner Familial Ovarian Cancer Registries (UKGRFOCR) UKFOCR was supported by a project grant from CRUK to Paul Pharoah. We thank Simon Gayther, Carole Pye, Patricia Harrington and Eva Wozniak for their contributions towards the UKFOCR. We'd like to acknowledge the Roswell Park Alliance Foundation for their continued support of the Gilda Radner Ovarian Family Cancer Registry. GRFOCR would like to acknowledge Lara Sucheston (Department of Cancer Prevention and Control) and Kunle Odunsi (Departments Gynecologic Oncology and Immunology). University of Pennsylvania (UPENN)Work is supported by grants from the Breast Cancer Research Foundation (to KLN), MacDonald Family Foundation (SMD) and Komen Foundation (SMD)