Evaluation of the XRCC1 gene as a phenotypic modifier in BRCA1/2 mutation carriers. Results from the consortium of investigators of modifiers of BRCA1/BRCA2

A. Osorio, R. L. Milne, R. Alonso, G. Pita, P. Peterlongo, A. Teulé, K. L. Nathanson, S. M. Domchek, T. Rebbeck, A. Lasa, I. Konstantopoulou, F. B. Hogervorst, S. Verhoef, M. F. Van Dooren, A. Jager, M. G E M Ausems, C. M. Aalfs, C. J. Van Asperen, M. Vreeswijk, Q. WaisfiszC. E. Van Roozendaal, M. J. Ligtenberg, D. F. Easton, S. Peock, M. Cook, C. T. Oliver, D. Frost, B. Curzon, D. G. Evans, F. Lalloo, R. Eeles, L. Izatt, R. Davidson, J. Adlard, D. Eccles, K. R. Ong, F. Douglas, S. Downing, C. Brewer, L. Walker, H. Nevanlinna, K. Aittomäki, F. J. Couch, Z. Fredericksen, N. M. Lindor, A. Godwin, C. Isaacs, M. A. Caligo, N. Loman, H. Jernström, G. Barbany-Bustinza, A. Liljegren, H. Ehrencrona, M. Stenmark-Askmalm, L. Feliubadaló, S. Manoukian, B. Peissel, D. Zaffaroni, B. Bonanni, S. Fortuzzi, O. T. Johannsson, G. Chenevix-Trench, X. C. Chen, J. Beesley, A. B. Spurdle, O. M. Sinilnikova, S. Healey, L. McGuffog, A. C. Antoniou, J. Brunet, P. Radice, J. Benítez

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Background: Single-nucleotide polymorphisms (SNPs) in genes involved in DNA repair are good candidates to be tested as phenotypic modifiers for carriers of mutations in the high-risk susceptibility genes BRCA1 and BRCA2. The base excision repair (BER) pathway could be particularly interesting given the relation of synthetic lethality that exists between one of the components of the pathway, PARP1, and both BRCA1 and BRCA2. In this study, we have evaluated the XRCC1 gene that participates in the BER pathway, as phenotypic modifier of BRCA1 and BRCA2. Methods: Three common SNPs in the gene, c.-77C>T (rs3213245) p.Arg280His (rs25489) and p.Gln399Arg (rs25487) were analysed in a series of 701 BRCA1 and 576 BRCA2 mutation carriers. Results: An association was observed between p.Arg280His-rs25489 and breast cancer risk for BRCA2 mutation carriers, with rare homozygotes at increased risk relative to common homozygotes (hazard ratio: 22.3, 95% confidence interval: 14.3-34, P
    Original languageEnglish
    Pages (from-to)1356-1361
    Number of pages5
    JournalBritish Journal of Cancer
    Volume104
    Issue number8
    DOIs
    Publication statusPublished - 12 Apr 2011

    Keywords

    • BRCA1
    • BRCA2
    • breast cancer
    • XRCC1

    Fingerprint

    Dive into the research topics of 'Evaluation of the XRCC1 gene as a phenotypic modifier in BRCA1/2 mutation carriers. Results from the consortium of investigators of modifiers of BRCA1/BRCA2'. Together they form a unique fingerprint.

    Cite this