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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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

Funding

FundersFunder number
Fondazione Italiana per la Ricerca sul Cancro
Universiteit Gent
Landspitali-University Hospital
National Breast Cancer Foundation
Starr Foundation
Breast Cancer Research Foundation
Ligue Contre le Cancer
Mayo Rochester
Instituto de Salud Carlos III
Ministero della Sanità, and Alleanza Contro il Cancro
Istituto Oncologico Veneto
Neye Foundation
Compagnia di San Paolo
National Institute for Health Research
Associazione Italiana per la Ricerca sul Cancro
Ministero della Salute
Cancer Foundation of Western Australia
IOVHBOCS
Mutua Madrileña and Marató TV Foundations
Petrov Institute of Oncology
University of Michigan Comprehensive Cancer Center
Ohio State University Clinical Cancer Genetics Program
Ministero dell’Istruzione, dell’Università e della Ricerca
Cancer Council NSW
Fonds De La Recherche Scientifique - FNRS
Komen Foundation for the Cure
Univerzita Karlova v Praze
Canadian Institutes of Health Research
NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research
NNPIO
Department of Biochemistry and Experimental Oncology, First Faculty of Medicine
Cancer Council Queensland
Russian Foundation for Basic Research08-04-00369-a, 09-04-90402-a
Columbia UniversityU01 CA69398
Seventh Framework Programme288704
National Cancer InstituteNO2-CP-11019-50, P50CA116201, N02-CP-65504, U01CA116167, ZIACP010144, U10CA027469, R01CA128978, U01CA069638, U01CA069417, R01CA122340, R01CA074415, U01CA069631, U01CA069446, U01CA069467, U10CA037517, U01CA069398
Huntsman Cancer InstituteU01 CA69446
Fonds Wetenschappelijk Onderzoek12051203
Dutch Cancer SocietyNKI1998-1854, NKI 2007-3756, NKI2004-3088
National Health and Medical Research Council454508
Northern California Cancer CenterU01 CA69417
Breast CancerP50 CA116201
National Institutes of HealthRFA-CA-06-503
Fox Chase Cancer CenterU01 CA69631
Research Triangle Institute Informatics Support-CenterN02PC45022-46
Cancer Care OntarioU01 CA69467
Ministerio de Sanidad, Consumo y Bienestar Social1.5.150.07, CR-MZ0 MOU 2005
Hospital Clínico San CarlosRD06/0020/0021, FIS 05/0864
Cancer Research UKC5047/A8385, C1287/A8874, C1287/A10118, C8197/A10123
Ministerstvo Školství, Mládeže a TělovýchovyMSM0021620808
University of MelbourneU01 CA69638
Deutsche Krebshilfegrant107054

    Keywords

    • BRCA1
    • BRCA2
    • Breast cancer
    • ERCC4

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