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

Ana Osorio*, Roger L. Milne, I. Rodriguez-Alonso, Guillermo Pita, Paolo Peterlongo, Alex Teule, Katherine L. Nathanson, Susan M. Domchek, Tim Rebbeck, Adriana Lasa, Irene Konstantopoulou, Frans B. L. Hogervorst, S. Verhoef, M. F. van Dooren, A. Jager, M. G. E. M. Ausems, Cora M. Aalfs, Christi J. van Asperen, M. van Vreeswijk, Quinten WaisfiszC. E. Van Roozendaal, Jack J. M. Ligtenberg, Douglas F. Easton, Susan Peock, Margaret Cook, Clare T. Oliver, Debra Frost, B. Curzon, D. Gareth Evans, Fiona Lalloo, Rosalind Eeles, Louise Izatt, Rosemarie Davidson, Julian Adlard, D. M. Eccles, Kai-ren Ong, Fiona Douglas, S. Downing, Alison C. Brewer, Cheryl L. Walker, Heli Nevanlinna, Kristiina Aittomaki, Fergus J. Couch, Zachary Fredericksen, Noralane M. Lindor, Andrew K. Godwin, C. Isaacs, Maria A. Caligo, Niklas Loman, H. Jernstrom, Gisela Barbany-Bustinza, Annelie Liljegren, Hans Ehrencrona, Marie Stenmark-Askmalm, Lidia Feliubadalo, Siranoush Manoukian, Bernard Peissel, Daniela Zaffaroni, Bernardo Bonanni, Stefano Fortuzzi, Oskar T. Johannsson, Georgia Chenevix-Trench, X-C Chen, Jonathan Beesley, Amanda B. Spurdle, Olga M. Sinilnikova, Catherine S. Healey, Lesley McGuffog, Antonis C. Antoniou, Joan Brunet, Paolo Radice, Javier Benitez

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.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.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
JournalBritish Journal of Cancer
Issue number8
Publication statusPublished - 12 Apr 2011


  • BRCA1
  • BRCA2
  • XRCC1
  • breast cancer


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