BRCA1 wild-type allele modifies risk of ovarian cancer in carriers of BRCA1 germ-line mutations

Sophie M. Ginolhac, Sophie Gad, Marilys Corbex, Brigitte Bressac-de-Paillerets, Agnès Chompret, Yves Jean Bignon, Jean Philippe Peyrat, Joelle Fournier, Christine Lasset, Sophie Giraud, Danièle Muller, Jean Pierre Fricker, Agnès Hardouin, Pascaline Berthet, Christine Maugard, Catherine Nogues, Rosette Lidereau, Michel Longy, Sylviane Olschwang, Christine ToulasRosine Guimbaud, Drakoulis Yannoukakos, Csilla Szabo, Francine Durocher, Anne Marie Moisan, Jacques Simard, Sylvie Mazoyer, Henry T. Lynch, David Goldgar, Dominique Stoppa-Lyonnet, Gilbert M. Lenoir, Olga M. Sinilnikova

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Strong inter- and intrafamilial variation of penetrance of breast and ovarian cancer is observed in BRCA1 mutation carriers. The wild-type copy of the BRCA1 gene is a plausible candidate as a cancer risk modifier given that the residual function corresponding to the intact BRCA1 allele may influence the process of tumor formation in BRCA1 carriers. Indeed, growing evidence is now becoming available on impaired reparation of double-strand DNA breaks in cells heterozygous for BRCA1 mutations, implying an enhanced mutability of BRCA1+/- cells. To determine whether certain variant forms of the wild-type BRCA1 allele are implicated in variation of the BRCA1-related cancer risk, their effect was studied in a panel of 591 women with BRCA1 germline mutations. We found that BRCA1 carriers with the wild-type BRCA1 copy bearing a common Gly1038 variant were at increased risk of ovarian cancer (hazards ratio, 1.50; 95% confidence interval, 1.03-2.19). The results of our study imply that a quite significant proportion of the interindividual variability in ovarian cancer penetrance in BRCA1 carriers may be explained by a common BRCA1 Gly1038 wild-type allele, given its high frequency (0.27).

Original languageEnglish (US)
Pages (from-to)90-95
Number of pages6
JournalCancer Epidemiology Biomarkers and Prevention
Volume12
Issue number2
StatePublished - Feb 1 2003

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Oncology

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    Ginolhac, S. M., Gad, S., Corbex, M., Bressac-de-Paillerets, B., Chompret, A., Bignon, Y. J., Peyrat, J. P., Fournier, J., Lasset, C., Giraud, S., Muller, D., Fricker, J. P., Hardouin, A., Berthet, P., Maugard, C., Nogues, C., Lidereau, R., Longy, M., Olschwang, S., ... Sinilnikova, O. M. (2003). BRCA1 wild-type allele modifies risk of ovarian cancer in carriers of BRCA1 germ-line mutations. Cancer Epidemiology Biomarkers and Prevention, 12(2), 90-95.