Rationale and hypothesis
Mutations in high-penetrance genes such as BRCA1 and BRCA2 predispose to breast cancer, and recently a number of low-penetrance breast cancer genes have also been identified. We reported that a coding SNP in the caspase-8 gene (CASP8 D302H) is associated with a reduced risk of breast cancer. More recently we identified a CASP8 4-SNP haplotype associated with an increased risk of breast cancer . A CASP8 promoter indel has been associated with breast cancer in an Asian population, although this has not been confirmed in Europeans. Our hypothesis is that these CASP8 variants may influence breast cancer susceptibility via effects on the apoptotic response.