BRCA mutations are changes in specific genes, BRCA1 and BRCA2, that significantly increase an individual’s risk of developing certain cancers. These genes normally function to prevent cancer by helping to repair damaged DNA within cells. When a mutation occurs in either BRCA1 or BRCA2, their ability to perform this repair is compromised, leading to an accumulation of genetic errors that can promote uncontrolled cell growth and tumor formation.
The Role of BRCA Genes
BRCA1 and BRCA2 genes are tumor suppressor genes, regulating cell growth and preventing tumor formation. They produce proteins that are involved in repairing damaged DNA, particularly double-strand breaks, which are among the most harmful types of DNA damage. This repair process is carried out through a highly accurate mechanism called homologous recombination.
BRCA1 plays a role in recognizing DNA damage and initiating the repair process by recruiting other necessary proteins. BRCA2 then helps in loading a protein called RAD51 onto the damaged DNA, a step that is fundamental for proper repair via homologous recombination. When a mutation occurs, this repair pathway is disrupted, allowing DNA errors to persist and potentially lead to cancer. Cellular genetic stability relies on the proper functioning of these genes.
Cancers Linked to BRCA Mutations
Mutations in the BRCA1 and BRCA2 genes are most commonly associated with an elevated risk of breast and ovarian cancers. For women with a BRCA1 or BRCA2 mutation, the lifetime risk of developing breast cancer can range from 45% to 85%, compared to 12% in the general population. The risk of ovarian cancer for women with these mutations is also higher, ranging from 10% to 58%, whereas the general population risk is less than 1% to 2%.
While primarily known for their link to breast and ovarian cancers, BRCA mutations also increase the risk for several other cancer types. Men with BRCA2 mutations have a higher risk of male breast cancer, with estimates ranging from 1.8% to 7.1% by age 70, compared to 0.1% in the general male population. Both BRCA1 and BRCA2 mutations are linked to an increased risk of prostate cancer in men, with BRCA2 mutations carrying a higher risk, up to 61% by age 80. Additionally, there is an elevated risk for pancreatic cancer, and an increased risk for melanoma, particularly with BRCA2 mutations.
Inheritance and Genetic Testing
BRCA mutations are inherited in an autosomal dominant pattern, meaning that if one parent carries a mutated copy of either the BRCA1 or BRCA2 gene, each child has a 50% chance of inheriting that mutation. This inheritance pattern applies to both sons and daughters, and the mutation can be passed down from either the mother’s or father’s side of the family. Understanding family history on both sides is important when assessing hereditary cancer risk.
Genetic testing for BRCA mutations involves a blood or saliva sample, as inherited mutations are present in nearly every cell of the body. Testing is recommended for individuals with a strong family history of breast, ovarian, pancreatic, or high-risk prostate cancer, especially if diagnosed at a younger age. People of Ashkenazi Jewish ancestry also have a higher likelihood of carrying specific BRCA mutations and may consider testing, especially with a family history of associated cancers. A positive result indicates an increased cancer risk but does not predict if or when cancer will develop.
Managing BRCA Mutation Risk
For individuals who test positive for a BRCA mutation, various strategies are available to manage their increased cancer risk. Enhanced surveillance involves more frequent and specialized screenings to detect cancer at an early, more treatable stage. This can include annual mammograms and breast MRIs for breast cancer screening, and transvaginal ultrasounds and blood tests (CA-125) for ovarian cancer screening. These screenings aim to maximize early detection, but do not prevent cancer from developing.
Prophylactic surgeries, which involve the removal of healthy tissue, are the most effective risk-reduction strategies. A prophylactic bilateral mastectomy, the surgical removal of both breasts, can significantly reduce breast cancer risk. Similarly, a risk-reducing bilateral salpingo-oophorectomy (RRSO), which is the removal of the ovaries and fallopian tubes, is recommended for women with BRCA mutations after childbearing is complete, as it reduces the risk of ovarian cancer and can also lower breast cancer risk in pre-menopausal women. Chemoprevention, using medications like tamoxifen or raloxifene, can also reduce breast cancer risk, particularly in BRCA2 carriers, by targeting estrogen receptor pathways.