1. The FA/BRCA pathway and breast cancer risk

1. Expanding the Fanconi anemia/breast cancer signaling pathwayThe Fanconi anemia/breast cancer signaling pathway plays a key role in the DNA damage response, which, in turn, may be altered in increased breast cancer risk. Genes with high-, moderate- or low-penetrance mutations for breast cancer and >15 Fanconi anemia genes (FANCs) encode for proteins of this pathway. In addition, modifiers of high-penetrance BRCA1/2 mutations are also components of the same pathway. Therefore, it is widely thought that additional genes in this pathway correspond to uncloned Fanconi anemia complementation groups and/or an unknown number of breast cancer genes. To gain a complete picture of this pathway and its link to disease, we have carried out protein-protein interaction screens for >50 components. These screens have identified several novel, high-confidence interaction partners, some of which are involved in biological processes such as cell cycle regulation and DNA damage response. Mutational and genotyping analyses are underway to define the potential role of these novel components in Fanconi anemia and/or breast cancer families without mutations in BRCA1/2.