The rs3834129 polymorphism and breast cancer risk in mutation carriers

• Published in: Breast cancer research and treatment 2010-07, Vol.125 (3), p.855-860
• Main Authors: Catucci, Irene, Verderio, Paolo, Pizzamiglio, Sara, Manoukian, Siranoush, Peissel, Bernard, Zaffaroni, Daniela, Roversi, Gaia, Ripamonti, Carla B., Pasini, Barbara, Barile, Monica, Viel, Alessandra, Giannini, Giuseppe, Papi, Laura, Varesco, Liliana, Martayan, Aline, Riboni, Mirko, Volorio, Sara, Radice, Paolo, Peterlongo, Paolo
• Format: Article
• Language: English
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-010-1068-8

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 and 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 mutation carriers. Of these, 740 carried a mutation and 467 a 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 and mutation carriers combined, 1.74 (95% CI: 1.24–2.46) for mutation carriers, and 1.09 (95% CI: 0.66–1.80) for 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 mutations but not in carriers of mutations.