Prioritizing Candidate Genetic Modifiers of BRCA1 and BRCA2 Using a Combinatorial Analysis of Global

Epidemiological evidence from different studies has shown that genes harboring sequence variations may modify breast cancer risk in BRCA1 and BRCA2 mutation carriers. Current attempts to identify genetic modifiers of BRCA1 and BRCA2 associated risk have focused on a candidate gene-based approach or the development of large genome-wide association studies. However, both methods have notable limitations. This chapter describes a novel approach for analyzing gene expression differences to prioritize candidate modifier genes for single nucleotide polymorphism association studies. The advantage that gives this strategy an edge over other candidate gene-based studies is its potential to identify candidate genes that interact with exogenous risk factors to cause or modify cancer, without detailed a priori knowledge of the molecular pathways involved.