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The Leu33Pro polymorphism in the ITGB3 gene does not modify BRCA1/2-associated breast or ovarian cancer risks: results from a multicenter study among 15,542 BRCA1 and BRCA2 mutation carriers

  • Epidemiology
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Abstract

Integrins containing the β3 subunit are key players in tumor growth and metastasis. A functional Leu33Pro polymorphism (rs5918) in the β3 subunit of the integrin gene (ITGB3) has previously been suggested to act as a modifier of ovarian cancer risk in Polish BRCA1 mutation carriers. To investigate the association further, we genotyped 9,998 BRCA1 and 5,544 BRCA2 mutation carriers from 34 studies from the Consortium of Investigators of Modifiers of BRCA1/2 for the ITGB3 Leu33Pro polymorphism. Data were analysed within a Cox-proportional hazards framework using a retrospective likelihood approach. There was marginal evidence that the ITGB3 polymorphism was associated with an increased risk of ovarian cancer for BRCA1 mutation carriers (per-allele Hazard Ratio (HR) 1.11, 95% CI 1.00–1.23, p-trend 0.05). However, when the original Polish study was excluded from the analysis, the polymorphism was no longer significantly associated with ovarian cancer risk (HR 1.07, 95% CI 0.96–1.19, p-trend 0.25). There was no evidence of an association with ovarian cancer risk for BRCA2 mutation carriers (HR 1.09, 95% CI 0.89–1.32). The polymorphism was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers. The ITGB3 Leu33Pro polymorphism does not modify breast or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers.

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Acknowledgements

Other contributing members of the CIMBA, the Consortium of Investigators of Modifiers of BRCA1/2-Related Cancer:

kConFab: Georgia Chenevix-Trench, Amanda B. Spurdle, Sue Healey, Xiaoqin Chen, Jonathan Beesley and kConFab Investigators; UCI: Susan L. Neuhausen, Yuan Chun Ding; MAYO: Fergus J. Couch, Xianshu Wang, Mary Karaus; MBCSG: Paolo Peterlongo, Siranoush Manoukian, Bernard Peissel, Bernardo Bonanni, Alessandra Viel, Paolo Radice; ModSQuaD: Csilla I. Szabo, Lenka Foretova, Michal Zikan, Bruce Poppe; NCI: Phuong L. Mai, Mark H. Greene; NICCC: Flavio Lejbkowicz, Gad Rennert; OCGN: Irene L. Andrulis, Hilmi Ozcelik, Gord Glendon; OUH: Mads Thomassen, Anne-Marie Gerdes, Torben A. Kruse; PBCS: Maria Adelaide Caligo, Grazia Lombardi; SMC: Yael Laitman, Bella Kaufman, Roni Milgrom, Shimrit Cohen, Ruth Gershoni-Baruch, Efrat Dragan, Eitan Friedman; SWE-BRCA: Niklas Loman, Per Karlsson, Hans Ehrencrona, Anna von Wachenfeldt; UPENN: Kurt D’Andrea, Susan M. Domchek, Katherine L. Nathanson, Timothy R. Rebbeck; IHCC: Pablo Serrano, Cezary Cybulski, Tadeusz Debniak, Bohdan Górski, Tomasz Byrski, Tomasz Huzarski, Jacek Gronwald; CNIO: Ana Osorio, Drakoulis Yannoukakos, Maite Cusido, Javier Benítez; DKFZ: Thomas Dünnebier; HEBON: Frans B.L. Hogervorst, Flora E. van Leeuwen, Maartje J. Hooning, Christi J. van Asperen, Peter Devilee, Marjolijn Ligtenberg, Rob B. van der Luijt, Cora M. Aalfs, Quinten Waisfisz, Marinus J. Blok; EMBRACE: Douglas Easton, Susan Peock, Margaret Cook, Clare Oliver, Debra Frost, Patricia Harrington, Gareth Evans, Fiona Lalloo, Rosalind Eeles, Louise Izatt, Carol Chu, Diana Eccles, Fiona Douglas, Carole Brewer, Lesley McGuffog; FCCC: Andrew K. Godwin; GEMO: Olga M. Sinilnikova, Dominique Stoppa-Lyonnet, Sylvie Mazoyer, Valérie Bonadona, Christine Lasset, Hélène Dreyfus, Dominique Leroux, Agnès Hardouin, Pascaline Berthet, Tetsuro Noguchi, Hagay Sobol, Etienne Rouleau, Catherine Nogues, Marc Frénay, Laurence Vénat-Bouvet, Evgeny Imyanitov; BCFR: Esther M. John, Saundra S. Buys, Mary Daly, John Hopper, Mary Beth Terry, Alexander Miron, Yosuf Yassin, David Goldgar; MUV: Christian F Singer, Daphne Gschwantler-Kaulich, Georg Pfeiler, Catharina Dressler; CBCS: Thomas v. O. Hansen, ILUH: Bjarni A. Agnarsson; MSKCC: Tomas Kirchhoff, Prodipto Pal, Kenneth Offit; GOG: Marion Piedmonte, Gustavo C. Rodriguez, Katie Wakeley, John F. Boggess, Jack Basil, Peter E. Schwartz, Stephanie V. Blank; OSU CCG: Amanda Ewart Toland; UTBCS: Anna Allavena; GC-HBOC: Beatrix Versmold, Barbara Wappenschmidt, Christoph Engel Alfons Meindl, Stefanie Engert, Norbert Arnold, Britta Fiebig, Bernhard H.F. Weber, Dieter Niederacher, Helmut Deissler, Christian Sutter, Karin Kast, Sabine Preisler-Adams; HCSC: Trinidad Caldes, Miguel de la Hoya; HEBCS: Heli Nevanlinna, Kristiina Aittomäki; INHERIT BRCAs: Jacques Simard; Honglin Song.

The CIMBA genotyping, data management and statistical analysis are supported by Cancer Research UK. ACA is a Cancer Research UK Senior Cancer Research Fellow. We thank Ellen Goode for organizing the distribution of the standard DNA plates, and Claudine Isaacs for access to the data from Georgetown University.

CIMBA collaborating centers:

Breast Cancer Family Registry (BCFR)

This work was supported by the National Cancer Institute, National Institutes of Health under RFA # CA-95-011 and through cooperative agreements with members of the Breast Cancer Family Registry and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Columbia University (U01 CA69398), Fox Chase Cancer Center (U01 CA69631), Huntsman Cancer Institute (U01 CA69446), Huntsman Cancer Institute (U01 CA69446), Northern California Cancer Center (U01 CA69417), University of Melbourne (U01 CA69638), and Research Triangle Institute Informatics Support Center (RFP No. N02PC45022-46). 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 Breast CFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the Breast CFR.

Copenhagen Breast Cancer Study (CBCS)

We wish to thank Bent Ejlertsen and Mette K. Andersen for their contributions to the study. This work was supported by the Neye Foundation.

Spanish National Cancer Centre (CNIO)

We thank R.M. Alonso for her excellent technical assistance. The samples studied at CNIO were recruited by the Spanish Consortium for the Study of Genetic Modifiers of BRCA1 and BRCA2. This study was partially supported by Mutua Madrileña and Marató TV Foundations.

Epidemiological study of BRCA1 & BRCA2 mutation carriers (EMBRACE)

DE is the PI of the study. EMBRACE Collaborating Centers are: Coordinating Centre, Cambridge: Susan Peock, Margaret Cook, Clare Oliver, Debra Frost. North of Scotland Regional Genetics Service, Aberdeen: Helen Gregory, Zosia Miedzybrodzka. Northern Ireland Regional Genetics Service, Belfast: Patrick Morrison. West Midlands Regional Clinical Genetics Service, Birmingham: Trevor Cole, Carole McKeown, Amy Taylor. South West Regional Genetics Service, Bristol: Alan Donaldson. East Anglian Regional Genetics Service, Cambridge: Joan Paterson. Medical Genetics Services for Wales, Cardiff: Alexandra Murray, Mark Rogers, Emma McCann. St James’s Hospital, Dublin & National Centre for Medical Genetics, Dublin: John Kennedy, David Barton. South East of Scotland Regional Genetics Service, Edinburgh: Mary Porteous. Peninsula Clinical Genetics Service. Exeter: Carole Brewer, Emma Kivuva, Anne Searle, Selina Goodman. West of Scotland Regional Genetics Service, Glasgow: Rosemarie Davidson, Victoria Murday, Nicola Bradshaw, Lesley Snadden, Mark Longmuir, Catherine Watt. South East Thames Regional Genetics Service, Guys Hospital London: Louise Izatt, Gabriella Pichert, Caroline Langman. North West Thames Regional Genetics Service. Harrow: Huw Dorkins. Leicestershire Clinical Genetics Service, Leicester: Julian Barwell. Yorkshire Regional Genetics Service, Leeds: Carol Chu, Tim Bishop, Julie Miller. Merseyside & Cheshire Clinical Genetics Service. Liverpool: Ian Ellis. Manchester Regional Genetics Service, Manchester: D Gareth Evans, Fiona Lalloo, Felicity Holt. North East Thames Regional Genetics Service, NE Thames: Alison Male, Anne Robinson. Nottingham Centre for Medical Genetics, Nottingham: Carol Gardiner. Northern Clinical Genetics Service, Newcastle: Fiona Douglas, Oonagh Claber. Oxford Regional Genetics Service, Oxford: Lisa Walker, Diane McLeod. The Institute of Cancer Research and Royal Marsden NHS Foundation Trust: Ros Eeles, Susan Shanley, Nazneen Rahman, Richard Houlston, Elizabeth Bancroft, Lucia D’Mello, Elizabeth Page, Audrey Ardern-Jones, Anita Mitra. North Trent Clinical Genetics Service, Sheffield: Jackie Cook, Oliver Quarrell, Cathryn Bardsley. South West Thames Regional Genetics Service, London: Shirley Hodgson, Sheila Goff, Glen Brice, Lizzie Winchester. Wessex Clinical Genetics Service. Princess Anne Hospital, Southampton: Diana Eccles, Anneke Lucassen, Gillian Crawford, Emma Tyler, Donna McBride. SP, MC, DF and CO are funded by Cancer Research-UK Grants C1287/A10118 and C1287/A8874. 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. RE/EB/L D’M are also supported by Cancer Research UK Grant C5047/A8385. DGE and FL are supported by an NIHR grant to the Biomedical Research Centre, Manchester.

Fox Chase Cancer Center (FCCC)

Andrew K. Godwin was funded by SPORE P-50CA83638, U01CA69631, 5U01CA113916, and the Eileen Stein Jacoby Fund.

German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC)

We thank all families for providing samples for this study. This work was supported by grants from the German Cancer Aid (Grant numbers 107054 and 107353).

The GEMO study (Genetic Modifiers of cancer risk in BRCA1/2 mutation carriers: Cancer Genetics Network “Groupe Génétique et Cancer”, Fédération Nationale des Centres de Lutte Contre le Cancer, France): We wish to thank all the GEMO collaborating members for their contribution to this study. The GEMO study was supported by the Ligue National Contre le Cancer and the Association “Le cancer du sein, parlons-en!” Award. GEMO Collaborating Centers are: Coordinating Centres, Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Hospitalier Universitaire de Lyon/Centre Léon Bérard, & UMR5201 CNRS, Université de Lyon, Lyon: Olga Sinilnikova, Laure Barjhoux, Sophie Giraud, Mélanie Léone, Sylvie Mazoyer; and INSERM U509, Service de Génétique Oncologique, Institut Curie, Paris: Dominique Stoppa-Lyonnet, Marion Gauthier-Villars, Claude Houdayer, Virginie Moncoutier, Muriel Belotti, Antoine de Pauw. Institut Gustave Roussy, Villejuif: Brigitte Bressac-de-Paillerets, Audrey Remenieras, Véronique Byrde, Olivier Caron, Gilbert Lenoir. Centre Jean Perrin, Clermont-Ferrand: Yves-Jean Bignon, Nancy Uhrhammer. Centre Léon Bérard, Lyon: Christine Lasset, Valérie Bonadona. Centre François Baclesse, Caen: Agnès Hardouin, Pascaline Berthet. Institut Paoli Calmettes, Marseille: Hagay Sobol, Violaine Bourdon, François Eisinger. Groupe Hospitalier Pitié-Salpétrière, Paris: Florence Coulet, Chrystelle Colas, Florent Soubrier. CHU de Arnaud-de-Villeneuve, Montpellier: Isabelle Coupier. Centre Oscar Lambret, Lille: Jean-Philippe Peyrat, Joëlle Fournier, Françoise Révillion, Philippe Vennin, Claude Adenis. Centre René Huguenin, St Cloud: Etienne Rouleau, Rosette Lidereau, Liliane Demange, Catherine Nogues. Centre Paul Strauss, Strasbourg: Danièle Muller, Jean-Pierre Fricker. Institut Bergonié, Bordeaux: Michel Longy, Nicolas Sevenet. Institut Claudius Regaud, Toulouse: Christine Toulas, Rosine Guimbaud, Laurence Gladieff, Viviane Feillel. CHU de Grenoble: Dominique Leroux, Hélène Dreyfus, Christine Rebischung. CHU de Dijon: Cécile Cassini, Laurence Olivier-Faivre. CHU de St-Etienne: Fabienne Prieur. Hôtel Dieu Centre Hospitalier, Chambéry: Sandra Fert Ferrer. Centre Antoine Lacassagne, Nice: Marc Frénay. CHU de Limoges: Laurence Vénat-Bouvet. Creighton University, Omaha, USA: Henry T. Lynch.

Gynecologic Oncology Group (GOG)

Participation was supported through funding provided by both intramural (Clinical Genetics Branch, DCEG) and extramural (Community Oncology and Prevention Trials Program—COPTRG) NCI programs. Genotyping of GOG DNA samples were performed by NCI’s Core Genotyping Facility. The technical expertise of Dr. Tim Sheehy and Ms. Amy Hutchinson is gratefully acknowledged.

Hospital Clinico San Carlos (HCSC)

This work was supported by grant RD06/0020/0021 from ISCIII, Spanish Ministry of Science and Innovation

Helsinki Breast Cancer Study (HEBCS)

We thank Drs. Carl Blomqvist and Kirsimari Aaltonen, and Tuomas Heikkinen and R. N. Hanna Jäntti for their help with the patient and sample data. The HEBCS study has been financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (110663), the Finnish Cancer Society, and the Sigrid Juselius Foundation.

Hereditary Breast and Ovarian cancer Working Group, the Netherland (HEBON)

Collaborating centers: Coordinating center: Netherlands Cancer Institute, Amsterdam: Frans Hogervorst, Senno Verhoef, Anouk Pijpe, Laura van ‘t Veer, Flora van Leeuwen, Matti Rookus; Erasmus Medical Center, Rotterdam: Margriet Collée, Ans van den Ouweland, Mieke Kriege, Mieke Schutte, Maartje Hooning, Caroline Seynaeve; Leiden University Medical Center, Leiden: Christi van Asperen, Juul Wijnen, Maaike Vreeswijk, Rob Tollenaar, Peter Devilee; Radboud University Nijmegen Medical Center, Nijmegen: Marjolijn Ligtenberg, Nicoline Hoogerbrugge; University Medical Center Utrecht, Utrecht: Margreet Ausems, Rob van der Luijt; Amsterdam Medical Center: Cora Aalfs, Theo van Os; VU University Medical Center, Amsterdam: Hans Gille, Quinten Waisfisz, Hanne Meijers-Heijboer; University Hospital Maastricht, Maastricht: Encarna Gomez-Garcia, Kees van Roozendaal, Marinus Blok; University Medical Center Groningen University: Jan Oosterwijk, Annemieke van der Hout, Marian Mourits; The Netherlands Foundation for the detection of hereditary tumours, Leiden, the Netherlands: Hans Vasen.

The HEBON study is supported by the Dutch Cancer Society grants NKI 1998-1854, NKI 2004-3088 and NKI 2007-3756.

Iceland, Landspitali—University Hospital (ILUH)

Group participation was supported by the Research Fund of Landspitali-University Hospital and the Icelandic association: „Walking for Breast Cancer Research”.

Interdisciplinary Health Research International Team Breast Cancer susceptibility (INHERIT)

Jacques Simard, Francine Durocher, Rachel Laframboise, Marie Plante, Centre Hospitalier Universitaire de Québec & Laval University,Quebec City, Canada;

Peter Bridge, Jilian Parboosingh, Molecular Diagnostic Laboratory, Alberta Children’s Hospital, Calgary, Canada;

Jocelyne Chiquette, Hôpital du Saint-Sacrement, Quebec City, Canada;

Bernard Lesperance, Roxanne Pichette, Hôpital du Sacré-Coeur de Montréal, Montréal, Canada.

Jacques Simard is Chairholder of the Canada Research Chair in Oncogenetics. This work was supported by the Canadian Institutes of Health Research for the «CIHR Team in Familial Risks of Breast Cancer» program.

The Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab)

We wish to thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (funded by NHMRC grants 145684, 288704 and 454508) for their contributions to this resource, and the many families who contribute to kConFab. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. ABS and GCT are supported by a NHMRC Senior Research and Senior Principal Research Fellowships, respectively.

Mayo Clinic (MAYO)

The study was supported by the Komen Foundation for the cure, NIH Sponsored Program of Research Excellence (SPORE) (CA116201), and NIH R01a (CA116167, CA128978 and CA122340).

Milan Breast Cancer Study Group (MBCSG)

MBCSG is supported by Fondazione Italiana per la Ricerca sul Cancro (FIRC, Special Project ‘‘Hereditary tumors’’) and Associazione Italiana per la Ricerca sul Cancro (AIRC). MBCSG acknowledges Marco Pierotti, Daniela Zaffaroni and Carla B. Ripamonti of the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, Monica Barile of the Istituto Europeo di Oncologia, Milan, Italy, Loris bernard and Laura Tizzoni of the Cogentech, Consortium for Genomic Technologies, Milan, Italy

Modifier Study of Quantitative Effects on Disease (ModSQuaD)

Collaborators: C.I. Szabo (Mayo Clinic College of Medicine, Rochester, MN); Michal Zikan, Petr Pohlreich, Zdenek Kleibl (First Faculty of Medicine, Charles University, Prague, Czech Republic); Lenka Foretova, Machackova Eva, and Lukesova Miroslava (Masaryk Memorial Cancer Institute, Brno, Czech Republic); Kathleen Claes, Kim De Leeneer, Bruce Poppe, Anne De Paepe (Ghent University, Ghent, Belgium).

C.I. Szabo is supported by Susan G. Komen Foundation Basic, Clinical, and Translational Research grant (BCTR0402923) and the Mayo Rochester Early Career Development Award for Non-Clinician Scientists; We acknowledge the contributions of Petr Pohlreich and Zdenek Kleibl (Department of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic) and the support of the Grant Agency of the Czech republic grant No. 301/08/P103 (to M.Z.). Lenka Foretova, Machackova Eva, and Lukesova Miroslava (Masaryk Memorial Cancer Institute, Brno, Czech Republic) are supported through the Ministry of Health of the CR grant—MZ0 MOU 2005. We acknowledge the contribution of Kim De Leeneer, Kathleen Claes, and Anne De Paepe. This research was supported by grant 1.5.150.07 from the Fund for Scientific Research Flanders (FWO) to Kathleen Claes and by grant 12051203 from the Ghent university to Anne De Paepe. Bruce Poppe is Senior Clinical Investigator of the Fund for Scientific Research of Flanders (FWO—Vlaanderen).

National Cancer Institute (NCI)

The research of Drs. MH Greene and PL Mai is 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. Genoptyping of NCI DNA samples were performed by NCI’s Core Genotyping Facility, Gaithersburg, MD.

N.N. Petrov Institute of Oncology (NNPIO)

Evgeny Imyanitov: RFBR grants (08-04-00369, 09-04-90402)

Ontario Cancer Genetics Network (OCGN)

We wish to thank Mona Gill, Lucine Collins, Nalan Gokgoz, Teresa Selander, Nayana Weerasooriya and members of the Ontario Cancer Genetics Network for their contributions to the study.

Ohio State University Clinical Cancer Center (OSU CCG)

This work was funded by the OSU Comprehensive Cancer Center. We thank Kevin Sweet and Caroline Craven for patient accrual and data management, the Human Genetics Sample Bank for sample preparation and the OSU Nucleic Acids Shared Resource for genotyping plate reads.

Odense University Hospital (OUH)

Dorthe Crüger and Lone Sunde are acknowledged for collecting clinical data from the Danish carriers.

Pisa Breast Cancer Study (PBCS)

Partly funded by Fondazione Cassa di Risparmio di Pisa (fellowship to Grazia Lombardi).

Sheba Medical Centre (SMC)

This work was in part funded by the Israel Cancer Association by a grant to Eitan Friedman

The Swedish BRCA1 and BRCA2 Study (SWE-BRCA)

Collaborators: Per Karlsson, Margareta Nordling, Annika Bergman and Zakaria Einbeigi, Gothenburg, Sahlgrenska University Hospital; Marie Stenmark-Askmalm and Sigrun Liedgren, Linkoping University Hospital; Ake Borg, Niklas Loman, Hakan Olsson, Ulf Kristoffersson, Helena Jernstrom, Katja Harbst and Karin Henriksson, Lund University Hospital; Annika Lindblom, Brita Arver, Anna von Wachenfeldt, Annelie Liljegren, Gisela Barbany-Bustinza and Johanna Rantala, Stockholm, Karolinska University Hospital; Beatrice Malmer, Henrik Gronberg, Eva-Lena Stattin and Monica Emanuelsson, Umea University Hospital; Hans Ehrencrona, Richard Rosenquist Brandell and Niklas Dahl, Uppsala University Hospital.

University of California Irvine (UCI)

This research was supported by NIH RO! CA74415 to SLN. We thank Linda Steele for participant accrual and data management.

University of Turin Breast Cancer Study (UTBCS)

The work of Anna Allavena was supported by Compagnia di San Paolo (Progetto Oncologia).

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Authors and Affiliations

  1. IHCC (International Hereditary Cancer Centre), Department of Genetics and Pathology, Pomeranian Medical University, Polabska 4, 70-115, Szczecin, Poland

    Anna Jakubowska & Jan Lubinski

  2. Department of Statistics and Econometrics, School of Economics and Management, University of Szczecin, Szczecin, Poland

    Dominik Rozkrut

  3. Cancer Research UK Genetic Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK

    Antonis Antoniou

  4. Division of Molecular Genome Analysis, Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Ute Hamann

Authors
  1. Anna Jakubowska
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  2. Dominik Rozkrut
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  3. Antonis Antoniou
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  4. Ute Hamann
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  5. Jan Lubinski
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Corresponding author

Correspondence to Anna Jakubowska.

Additional information

This study is conducted on behalf of CIMBA, the Consortium of Investigators of Modifiers of BRCA1/2-Related Cancer: kConFab, UCI, MAYO, MBCSG, ModSQuaD, NCI, NICCC, OCGN, OUH, PBCS, SMC, SWE-BRCA, UPENN, IHCC, CNIO, DKFZ, HEBON, EMBRACE, FCCC, GEMO, BCFR, MUV, CBCS, MSKCC, GOG, OSU CCG, UTBCS, GC-HBOC, HCSC, HEBCS, INHERIT BRCAs.

Contributing and collaborating members of the CIMBA consortium are detailed in Acknowledgements.

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Jakubowska, A., Rozkrut, D., Antoniou, A. et al. The Leu33Pro polymorphism in the ITGB3 gene does not modify BRCA1/2-associated breast or ovarian cancer risks: results from a multicenter study among 15,542 BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat 121, 639–649 (2010). https://doi.org/10.1007/s10549-009-0595-7

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