BRCA1BRCA2

BRCA1 and BRCA2 are human genes that encode proteins essential for repairing DNA double-strand breaks by homologous recombination. This function helps maintain genomic stability and acts as a barrier to cancer development. Germline pathogenic variants in either gene confer hereditary breast and ovarian cancer (HBOC) syndrome and are inherited in an autosomal dominant pattern with variable penetrance. BRCA1 is located on chromosome 17 and BRCA2 on chromosome 13.

Individuals with BRCA1 variants have an increased risk of breast cancer and ovarian cancer and may develop tumors that are biologically distinct from sporadic cases. BRCA2 variants also raise breast cancer risk and are associated with an elevated risk of male breast cancer as well as pancreatic and prostate cancers. Together, BRCA1 and BRCA2 mutations raise risk for several cancers and have implications for family members who may carry the same variants.

Genetic testing can identify pathogenic or likely pathogenic BRCA1/BRCA2 variants and is accompanied by genetic counseling. Results are typically categorized as pathogenic or likely pathogenic, variant of uncertain significance, or benign. Management options include enhanced cancer surveillance, risk-reducing surgeries such as prophylactic salpingo-oophorectomy or mastectomy, and consideration of targeted therapies for BRCA-mutant cancers.

PARP inhibitors, such as olaparib, niraparib, and rucaparib, exploit BRCA1/BRCA2 deficiency and are approved for certain BRCA-associated breast, ovarian, pancreatic, and prostate cancers. The genes were discovered in the 1990s, with BRCA1 identified in 1994 and BRCA2 in 1995; founder mutations have been reported in several populations, notably BRCA1 185delAG, BRCA1 5382insC, and BRCA2 6174delT in Ashkenazi Jewish populations.