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Synergism between BRCA1 Mutation and Impaired Estrogen Signaling in Oxidative Stress Modulation Makes Estrogen Responsive Tissues (Breast) More Susceptible to Develop Cancer

Aarifa Nazmeen and Smarajit Maiti

Specific inherited mutations in BRCA1 increases the risk of female breast and ovarian cancers. BRCA1 critically maintains genome stability and cell cycle progression. BRCA1 is a well-known tumor suppressor gene; germline mutations in this gene confer increased susceptibility to developing breast and ovarian cancer. Though breast cancer associated with BRCA1 mutations were considered sporadic for mostly being Erα(-). Significant numbers of Erα(+) BRCA1 mutated breast cancer patients were also discovered. There are two questions prevailing with BRCA1 breast cancers. Why BRCA1 related patients have higher risk for cancer development mainly in estrogen responsive tissues such as breast and ovary. And the second is, the therapeutic approach for Erα(+) BRCA1 breast cancers may not be same as Erα(-) BRCA1 cancers. Recently BRCA1 in context with oxidative stress is been widely studied. The association of BRCA1 and cancers in estrogen responsive tissues may be explained by BRCA1, estrogen and ER cooperation mediated by oxidative stress.