title: BRCA1 wild-type allele modifies risk of ovarian cancer in carriers of BRCA1 germ-line mutations.
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 germ-line 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).
authors.affiliation: Centre National de la Recherche Scientifique, UMR 5641, Lyon, France.
authors.forename: Sophie M
authors.initials: SM
authors.lastname: Ginolhac
authors.forename: Sophie
authors.initials: S
authors.lastname: Gad
authors.forename: Marilys
authors.initials: M
authors.lastname: Corbex
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bressac-De-Paillerets
authors.forename: Agnès
authors.initials: A
authors.lastname: Chompret
authors.forename: Yves-Jean
authors.initials: YJ
authors.lastname: Bignon
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Peyrat
authors.forename: Joelle
authors.initials: J
authors.lastname: Fournier
authors.forename: Christine
authors.initials: C
authors.lastname: Lasset
authors.forename: Sophie
authors.initials: S
authors.lastname: Giraud
authors.forename: Danièle
authors.initials: D
authors.lastname: Muller
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Fricker
authors.forename: Agnès
authors.initials: A
authors.lastname: Hardouin
authors.forename: Pascaline
authors.initials: P
authors.lastname: Berthet
authors.forename: Christine
authors.initials: C
authors.lastname: Maugard
authors.forename: Catherine
authors.initials: C
authors.lastname: Nogues
authors.forename: Rosette
authors.initials: R
authors.lastname: Lidereau
authors.forename: Michel
authors.initials: M
authors.lastname: Longy
authors.forename: Sylviane
authors.initials: S
authors.lastname: Olschwang
authors.forename: Christine
authors.initials: C
authors.lastname: Toulas
authors.forename: Rosine
authors.initials: R
authors.lastname: Guimbaud
authors.forename: Drakoulis
authors.initials: D
authors.lastname: Yannoukakos
authors.forename: Csilla
authors.initials: C
authors.lastname: Szabo
authors.forename: Francine
authors.initials: F
authors.lastname: Durocher
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Moisan
authors.forename: Jacques
authors.initials: J
authors.lastname: Simard
authors.forename: Sylvie
authors.initials: S
authors.lastname: Mazoyer
authors.forename: Henry T
authors.initials: HT
authors.lastname: Lynch
authors.forename: David
authors.initials: D
authors.lastname: Goldgar
authors.forename: Dominique
authors.initials: D
authors.lastname: Stoppa-Lyonnet
authors.forename: Gilbert M
authors.initials: GM
authors.lastname: Lenoir
authors.forename: Olga M
authors.initials: OM
authors.lastname: Sinilnikova
mesh_terms: D000328:Adult; D000367:Age Factors; D000483:Alleles; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics; D002170:Canada / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D005787:Gene Frequency / Q000235:genetics; D019398:Genes, BRCA1 / Q000502:physiology; D005819:Genetic Markers / Q000235:genetics; D018095:Germ-Line Mutation / Q000235:genetics*; D006115:Greece / Q000453:epidemiology; D006579:Heterozygote; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics*; D010298:Parity / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D016387:Women's Health
chemical_list: D005819:Genetic Markers