Role of ATM in BRCA or non-BRCA cancer susceptibility
The significance of BRCA1 and BRCA2 in breast cancer families without epithelial ovarian cancer or male breast cancer is modest. It is conceivable that genetic predisposition to breast cancer includes other factors and mechanisms. The ataxia-telangiectasia (AT) gene (ATM) predisposes heterozygotes to cancer, particularly breast cancer. 6.6% of all breast cancers occur in women who are AT mutation carriers. The reported increased breast cancer risk for AT family members has been most evident among younger women. We wish to elucidate the contribution of ATM mutations to cancer susceptibility in BRCA and non-BRCA breast tumors. Comprehensive typing of single nucleotide polymorphism will likely illuminate the complex interactions of variants with genes involved in DNA repair, detoxification and hormone metabolism. Our aim is to understand the cellular functions of ATM and how mutations in ATM increase risk to cancer predisposition in carriers of BRCA mutations.