title: The CASP8 rs3834129 polymorphism and breast cancer risk in BRCA1 mutation carriers.
abstract: The rs3834129 polymorphism, in the promoter of CASP8 gene, has been recently reported as associated with breast cancer risk in the general population, with the minor allele del having a protective effect. Some of the genetic variants found associated with breast cancer risk were reported as risk modifiers in individuals with mutations in BRCA1 and BRCA2 genes. Here, we tested the effect of the rs3834129 del allele on breast cancer risk in BRCA mutation carriers. The rs3834129 was genotyped in a total of 1,207 Italian female BRCA mutation carriers. Of these, 740 carried a BRCA1 mutation and 467 a BRCA2 mutation. Overall, 699 were affected with breast cancer and 508 were unaffected. When considering class 1 (loss-of-function) BRCA mutations, hazard ratios estimated by weighted multivariable Cox regression model, for individuals with at least one copy of the del allele, were 1.46 (95% confidence interval (CI): 1.08-1.99) for BRCA1 and BRCA2 mutation carriers combined, 1.74 (95% CI: 1.24-2.46) for BRCA1 mutation carriers, and 1.09 (95% CI: 0.66-1.80) for BRCA2 mutation carriers. These results suggest that the minor allele del of rs3834129 is associated under a dominant model with increased breast cancer risk in carriers of BRCA1 mutations but not in carriers of BRCA2 mutations.
authors.affiliation: IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Catucci
authors.forename: Paolo
authors.initials: P
authors.lastname: Verderio
authors.forename: Sara
authors.initials: S
authors.lastname: Pizzamiglio
authors.forename: Siranoush
authors.initials: S
authors.lastname: Manoukian
authors.forename: Bernard
authors.initials: B
authors.lastname: Peissel
authors.forename: Daniela
authors.initials: D
authors.lastname: Zaffaroni
authors.forename: Gaia
authors.initials: G
authors.lastname: Roversi
authors.forename: Carla B
authors.initials: CB
authors.lastname: Ripamonti
authors.forename: Barbara
authors.initials: B
authors.lastname: Pasini
authors.forename: Monica
authors.initials: M
authors.lastname: Barile
authors.forename: Alessandra
authors.initials: A
authors.lastname: Viel
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giannini
authors.forename: Laura
authors.initials: L
authors.lastname: Papi
authors.forename: Liliana
authors.initials: L
authors.lastname: Varesco
authors.forename: Aline
authors.initials: A
authors.lastname: Martayan
authors.forename: Mirko
authors.initials: M
authors.lastname: Riboni
authors.forename: Sara
authors.initials: S
authors.lastname: Volorio
authors.forename: Paolo
authors.initials: P
authors.lastname: Radice
authors.forename: Paolo
authors.initials: P
authors.lastname: Peterlongo
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D053181:Caspase 8 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007558:Italy; D009154:Mutation; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D012306:Risk
chemical_list: D053181:Caspase 8