Disease family history and modification of breast cancer risk in common BRCA2 variants.
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.
Seymour
Ian Jonathan
IJ
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), 47014 Meldola (FC), Italy.
Casadei
Silvia
S
Zampiga
Valentina
V
Rosato
Simonetta
S
Danesi
Rita
R
Falcini
Fabio
F
Strada
Miria
M
Morini
Nori
N
Naldoni
Carlo
C
Paradiso
Angelo
A
Tommasi
Stefania
S
Schittulli
Francesco
F
Amadori
Dino
D
Calistri
Daniele
D
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