Role of CASP8 D302H and other apoptosis gene variants in breast cancer

It is well established that perturbations in high penetrance genes such as BRCA1 and BRCA2 predispose to breast cancer. However, low penetrance genes are still under investigation. Some apoptotic genes (for example, BIRC5, BCL2, DR4 and DR5) have been implicated, and we reported that a coding single nucleotide polymorphism (SNP) in the caspase 8 gene (CASP8 D302H) is associated with a reduced risk of breast cancer [1]. We hypothesise that CASP8 and other apoptotic genes may play an important role in breast cancer susceptibility. The objectives were to study the functional effect of CASP8 D302H on apoptosis, and to perform a case-control analysis of other CASP8 variants to determine their effect on breast cancer susceptibility.