title: Disease family history and modification of breast cancer risk in common BRCA2 variants.
abstract: A number of BRCA1 and BRCA2 polymorphisms have been extensively studied in order to test their association with breast cancer risk. Subsequently, discordant results were reported. In the present study, the genotypes of one BRCA1 (Q356R) and three BRCA2 (203G>A, N372H, IVS21-66T>C) common variants were evaluated in a series of 252 breast cancer patients, 155 age-matched controls and analysed in relation to family history (low- or high-risk) and BRCA1/2 mutation status. A complete analysis of the BRCA1/2 coding regions was performed on the 217 women from high-risk families and 44 BRCA1/2 mutation carriers were identifed. According to a dominant inheritance model, the BRCA2 IVS21-66T>C variant showed a 1.79-fold (95% CI, 1.16-2.78; P=0.009) increased breast cancer risk for the overall series. The BRCA2 N372H polymorphism was associated with a 2.29-fold (95% CI, 1.16-4.49; P=0.016) increased risk in the subgroup of high-risk families with no BRCA1/2 mutations. Conversely, the BRCA1 Q356R and BRCA2 203G>A polymorphisms did not show any significant associations with breast cancer risk. In conclusion, the analysis of some BRCA2 variants could help to identify women at a higher risk of developing breast cancer who could be candidates for chemoprevention protocols.
authors.affiliation: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), 47014 Meldola (FC), Italy.
authors.forename: Ian Jonathan
authors.initials: IJ
authors.lastname: Seymour
authors.forename: Silvia
authors.initials: S
authors.lastname: Casadei
authors.forename: Valentina
authors.initials: V
authors.lastname: Zampiga
authors.forename: Simonetta
authors.initials: S
authors.lastname: Rosato
authors.forename: Rita
authors.initials: R
authors.lastname: Danesi
authors.forename: Fabio
authors.initials: F
authors.lastname: Falcini
authors.forename: Miria
authors.initials: M
authors.lastname: Strada
authors.forename: Nori
authors.initials: N
authors.lastname: Morini
authors.forename: Carlo
authors.initials: C
authors.lastname: Naldoni
authors.forename: Angelo
authors.initials: A
authors.lastname: Paradiso
authors.forename: Stefania
authors.initials: S
authors.lastname: Tommasi
authors.forename: Francesco
authors.initials: F
authors.lastname: Schittulli
authors.forename: Dino
authors.initials: D
authors.lastname: Amadori
authors.forename: Daniele
authors.initials: D
authors.lastname: Calistri
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005192:Family Health; D005260:Female; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D011110:Polymorphism, Genetic