Evaluation of a candidate breast cancer associated SNP in ERCC4 as a risk modifier in BRCA1 and BRCA2 mutation carriers. Results from the consortium of investigators of modifiers of BRCA1/BRCA2 (CIMBA)

A. Osorio, R. L. Milne, G. Pita, P. Peterlongo, T. Heikkinen, J. Simard, G. Chenevix-Trench, A. B. Spurdle, J. Beesley, X. Chen, S. Healey, S. L. Neuhausen, Y. C. Ding, F. J. Couch, X. Wang, N. Lindor, S. Manoukian, M. Barile, A. Viel, L. TizzoniC. I. Szabo, L. Foretova, M. Zikan, K. Claes, M. H. Greene, P. Mai, G. Rennert, F. Lejbkowicz, O. Barnett-Griness, I. L. Andrulis, H. Ozcelik, N. Weerasooriya, A. M. Gerdes, M. Thomassen, D. G. Cruger, M. A. Caligo, E. Friedman, B. Kaufman, Y. Laitman, S. Cohen, T. Kontorovich, R. Gershoni-Baruch, E. Dagan, H. Jernström, M. S. Askmalm, B. Arver, B. Malmer, S. M. Domchek, K. L. Nathanson, J. Brunet, T. Ramón Y Cajal, D. Yannoukakos, U. Hamann, F. B.L. Hogervorst, S. Verhoef, E. B.Gómez Garcíla, J. T. Wijnen, A. Van Den Ouweland, D. F. Easton, S. Peock, M. Cook, C. T. Oliver, D. Frost, C. Luccarini, D. G. Evans, F. Lalloo, R. Eeles, G. Pichert, J. Cook, S. Hodgson, P. J. Morrison, F. Douglas, A. K. Godwin, O. M. Sinilnikova, L. Barjhoux, D. Stoppa-Lyonnet, V. Moncoutier, S. Giraud, C. Cassini, L. Olivier-Faivre, F. Révillion, J. P. Peyrat, D. Muller, J. P. Fricker, H. T. Lynch, E. M. John, S. Buys, M. Daly, J. L. Hopper, M. B. Terry, A. Miron, Y. Yassin, D. Goldgar, C. F. Singer, D. Gschwantler-Kaulich, G. Pfeiler, A. C. Spiess, Thomas V.O. Hansen, O. T. Johannsson, T. Kirchhoff, K. Offit, K. Kosarin, M. Piedmonte, G. C. Rodriguez, K. Wakeley, J. F. Boggess, J. Basil, P. E. Schwartz, S. V. Blank, A. E. Toland, M. Montagna, C. Casella, E. N. Imyanitov, A. Allavena, R. K. Schmutzler, B. Versmold, C. Engel, A. Meindl, N. Ditsch, N. Arnold, D. Niederacher, H. Deiler, B. Fiebig, R. Varon-Mateeva, D. Schaefer, U. G. Froster, T. Caldes, M. De La Hoya, L. McGuffog, A. C. Antoniou, H. Nevanlinna, P. Radice, J. Benítez

Research output: Contribution to journalArticlepeer-review

Abstract

Background: In this study we aimed to evaluate the role of a SNP in intron 1 of the ERCC4 gene (rs744154), previously reported to be associated with a reduced risk of breast cancer in the general population, as a breast cancer risk modifier in BRCA1 and BRCA2 mutation carriers. Methods: We have genotyped rs744154 in 9408 BRCA1 and 5632 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and assessed its association with breast cancer risk using a retrospective weighted cohort approach. Results: We found no evidence of association with breast cancer risk for BRCA1 (per-allele HR: 0.98, 95% CI: 0.93-1.04, P0.5) or BRCA2 (per-allele HR: 0.97, 95% CI: 0.89-1.06, P0.5) mutation carriers. Conclusion: This SNP is not a significant modifier of breast cancer risk for mutation carriers, though weak associations cannot be ruled out.

Original languageEnglish
Pages (from-to)2048-2054
Number of pages7
JournalBritish Journal of Cancer
Volume101
Issue number12
DOIs
StatePublished - Dec 2009

Bibliographical note

Funding Information:
MAYO study is supported in part by National Institute of Health Grants CA116167, CA122340, CA128978, a Sponsored Program of Research Excellence (SPORE) grant in Breast Cancer P50 CA116201, a grant from the Breast Cancer Research Foundation, and a grant from the Komen Foundation for the Cure.

Funding Information:
Interdisciplinary Health Research International Team Breast Cancer Susceptibility (INHERIT BRCAs): Jacques Simard, Francine Durocher, Rachel Laframboise, Marie Plante, Centre Hospitalier Universitaire de Quebec and Laval University, Quebec, Canada; Peter Bridge, Jilian Parboosingh, Molecular Diagnostic Laboratory, Alberta Children’s Hospital, Calgary, Canada; Jocelyne Chiquette, Hôpital du Saint-Sacrement, Quebec, Canada; Bernard Lesperance, Hôpital du Sacré-Cœur de Montréal, Montréal, Canada. Jacques Simard-JS 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.

Funding Information:
Epidemiological study of BRCA1 and BRCA2 mutation carriers (EMBRACE): EMBRACE is supported by Cancer Research UK Grants C1287/A10118 and C1287/A8874. CL is supported by Cancer Research UK Grant C8197/A10123. 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

Funding Information:
AC Antoniou is a Cancer Research UK Senior Cancer Research Fellow, L McGuffog, the CIMBA genotyping and data management are funded by Cancer Research UK.

Funding Information:
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. DE is the PI of the study. EMBRACE collaborating centres are: Coordinating Centre, Cambridge: Susan Peock, Margaret Cook, Clare Oliver, Debra Frost. North of Scotland Regional Genetics Service, Aberdeen: Zosia Miedzy-brodzka, Helen Gregory. 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 and 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 and 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, Sarah Durell. 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, Jennifer Wiggins, Elena Castro. 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.

Funding Information:
The Ohio State University Clinical Cancer Genetics Program (OSU CCG): This work was funded by the OSU Comprehensive Cancer Center. We thank K Sweet and C 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.

Funding Information:
Memorial Sloan-Kettering Cancer Center (MSKCC): acknowledges the support of ‘Breast Cancer Research Foundation, Starr Foundation, and the Niehaus Cancer Research Initiative’.

Funding Information:
SL Neuhausen and YC Ding were supported by NIH CA74415.

Funding Information:
The Copenhagen Breast Cancer Study (CBCS) is supported by the Neye Foundation.

Funding Information:
The Kathleen Cunningham Consortium for Research into Familial Breast Cancer (kConFab): We 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 is an NHMRC Senior Research Fellow, and GCT is an NHMRC Senior Principal Research Fellow.

Funding Information:
GC-HBOC is supported by a grant of the German Cancer Aid (grant107054) to RKS. We thank Juliane Köhler for her excellent technical assistance and the centres of the GC-HBOC for providing samples and clinical data.

Funding Information:
Hospital Clínico San Carlos (HCSC): T Caldes and M de Hoya are funded by RD06/0020/0021, FIS 05/0864 (ISCIII, Spain) and FMM 06.

Funding Information:
CI Szabo is supported by 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 Research Project of the Ministry of Education, Youth, and Sports of the Czech Republic grant MSM0021620808 (to MZ, Zdenek Kleibl, and Petr Pohlreich). Lenka Foretova, Machackova Eva, and Lukesova Miroslava’s are supported through the Ministry of Health grant CR-MZ0 MOU 2005. We acknowledge the contribution of Kim De Leeneer, Bruce Poppe 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).

Funding Information:
NN Petrov Institute of Oncology (NNPIO): Supported by grants from the Russian Foundation for Basic Research (grants 08-04-00369-a and 09-04-90402-a).

Funding Information:
Gynecologic Oncology group (GOG): This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office (CA 27469) and the Gynecologic Oncology Group Statistical and Data Center (CA 37517).

Funding Information:
Iceland Landspitali – University Hospital study (IUH) is supported by the Research Fund of Landspitali-University Hospital and the Walk together for breast cancer research.

Funding Information:
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 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 centres are: Coordinating Centres, Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Hospices Civils de Lyon/Centre Léon Bérard and 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 Franc¸ois Baclesse, Caen: Agnès Hardouin, Pascaline Berthet. Institut Paoli Calmettes, Marseille: Hagay Sobol, Violaine Bourdon, Franc¸ois Eisinger. Groupe Hospitalier Pitié-Salpétrière, Paris: Florence Coulet, Chrystelle Colas, Florent Soubrier. CHU de Arnaud-de-Villeneuve, Montpellier: Isabelle

Funding Information:
The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON): HEBON collaborating centres: Coordinating centre: 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: Rob Tollenaar, Christi van Asperen, Juul Wijnen, Maaike Vreeswijk, Peter Devilee; Radboud University Nijmegen Medical Center, Nijmegen: Nicoline Hoogerbrugge, Marjolijn Ligtenberg; University Medical Center Utrecht, Utrecht: Margreet Ausems, Rob van der Luijt; Amsterdam Medical Center: Cora Aalfs, Theo van Os; VU University Medical Center, Amsterdam: Hanne Meijers-Heijboer, Hans Gille; University Hospital Maastricht, Maastricht: Encarna Gomez-Garcia, Rien Blok. The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI 2007-3756.

Funding Information:
Spanish National Cancer Centre (CNIO): We thank RM 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.

Funding Information:
Istituto Oncologico Veneto (IOVHBOCS): The study was supported by the Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR), Ministero della Sanità, and Alleanza Contro il Cancro.

Funding Information:
Breast Cancer Family Registry (Breast CFR): 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 and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Columbia University (U01 CA69398), Fox Chase Cancer Center (U01 CA69631), 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 centres in the Breast CFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the Breast CFR.

Funding Information:
Milan Breast Cancer Study Group (MGCSG). MBCSG is supported by grants from Fondazione Italiana per la Ricerca sul Cancro (FIRC, Special Project ‘Hereditary tumors’), Associazione Italiana per la Ricerca sul Cancro (AIRC) and the Italian Ministry of Health. MBCSG acknowledges Marco Pierotti, Bernard Peissel, Daniela Zaffaroni and Carla B Ripamonti of the Fondazione IRCCS Istituto Nazionale dei Tumori,Milan, Italy, Bernardo Bonanni of the Istituto Europeo di Oncologia, Milan, Italy and Loris Bernard of the Cogentech, Consortium for Genomic Technologies, Milan, Italy.

Funding Information:
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. Genotyping of NCI DNA samples was performed by NCI’s Core Genotyping Facility.

Funding Information:
University of Turin Breast Cancer Study (UTBCS): The work of Anna Allavena has been supported by Compagnia di San Paolo (Progetto Oncologia).

Keywords

  • BRCA1
  • BRCA2
  • Breast cancer
  • ERCC4

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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