BRCA2

About BRCA2

BRCA2 Breast Cancer 2 on chromosome 13q13.1 works with BRCA1 and PALB2 in homologous recombination DNA repair, where the BRCA2 protein loads the RAD51 recombinase onto single stranded DNA at sites of double strand breaks. Inherited pathogenic variants raise the lifetime risk of breast and ovarian cancer, generally with somewhat lower ovarian cancer risk than BRCA1, and also increase the risk of pancreatic cancer, prostate cancer, and male breast cancer. BRCA2 associated breast cancers are more often hormone receptor positive than BRCA1 associated tumors. The Ashkenazi Jewish founder variant 6174delT is one of three well known founder variants in that population. Inheriting pathogenic variants in both copies of BRCA2 causes a form of Fanconi anemia, FANCD1, with bone marrow failure and early childhood cancers. The gene was identified in 1995. Like BRCA1 deficient tumors, BRCA2 deficient cancers are sensitive to platinum chemotherapy and PARP inhibitors such as olaparib, which is approved for several BRCA mutated cancers.