The BRCA1 gene is a segment of DNA found in every human cell. It maintains the stability of a person’s genetic material and provides instructions for creating a protein that contributes to normal cellular processes.
The Role of BRCA1
The BRCA1 gene’s healthy function involves producing a protein that acts as a tumor suppressor. This protein repairs damaged DNA. DNA strands can break from factors like radiation exposure or during genetic material exchange before cell division.
The BRCA1 protein works within the BRCA1-associated genome surveillance complex (BASC). This complex identifies damaged DNA and mends breaks. Its activity is particularly important in homologous recombination, an “error-free” DNA repair mechanism using a healthy DNA sequence as a template. It also influences gene expression in response to cellular stress and DNA damage, preventing genetic alterations that could lead to abnormal cell growth.
How BRCA1 Mutations Increase Cancer Risk
A BRCA1 gene mutation impairs its ability to repair damaged DNA. Errors accumulate in the genetic code, increasing unchecked cell division, a hallmark of cancer. Such mutations do not guarantee cancer development but significantly elevate the risk.
BRCA1 mutations increase the risk of specific cancers. For women, lifetime breast cancer risk with a BRCA1 mutation ranges from 45% to 85%, compared to about 12% in the general population. This includes a higher likelihood of more aggressive triple-negative breast cancer. Lifetime ovarian cancer risk for women with a BRCA1 mutation is approximately 10% to 46%.
Men with BRCA1 mutations also face elevated risks, though lower for breast cancer than women, with a lifetime risk of about 1%. Beyond breast and ovarian cancers, BRCA1 mutations link to an increased risk of prostate cancer, ranging from 7% to 26% by age 80. Pancreatic cancer, melanoma, and a rare type of endometrial cancer (uterine serous carcinoma) may also have increased risks.
Understanding BRCA1 Genetic Testing
Genetic testing for BRCA1 mutations identifies gene changes that might increase cancer risk. Candidates typically include individuals with a personal or family history of breast, ovarian, tubal, or peritoneal cancer, or those with ancestry linked to BRCA1 mutations (e.g., Ashkenazi Jewish heritage). Testing often begins with a family member diagnosed with a BRCA-related cancer to identify a specific mutation.
Testing usually involves a blood or saliva sample. DNA from the sample is analyzed to detect harmful BRCA1 gene changes. Results can be positive (a detected mutation), negative (no known mutation found), or a variant of uncertain significance (a change found but its effect on cancer risk is unclear).
Genetic counseling is an important step before and after BRCA1 testing. A genetic counselor or trained healthcare professional helps individuals understand if testing is appropriate, discusses benefits and limitations, and interprets results. They also provide guidance on managing cancer risk based on test outcomes.
Strategies for Managing BRCA1-Related Risk
Individuals with a known BRCA1 mutation or a strong family history of BRCA-related cancers have several options for managing their increased risk. These strategies aim for early detection or risk reduction. Enhanced screening protocols include annual breast MRI (from age 25), often with a yearly mammogram (from age 30), and clinical breast exams every 6-12 months. For ovarian cancer, surveillance may involve transvaginal ultrasounds and CA-125 blood tests, although their effectiveness in early detection is limited.
Risk-reducing surgeries are another option. A prophylactic mastectomy, which is the surgical removal of healthy breast tissue, can reduce breast cancer risk by approximately 90%. While significantly lowering risk, it is not a guarantee against cancer, as some breast tissue may remain. For ovarian cancer, a risk-reducing salpingo-oophorectomy (RRSO), removal of both ovaries and fallopian tubes, is strongly recommended, typically between ages 35-40 for BRCA1 carriers after childbearing. This procedure reduces the risk of ovarian cancer, ovarian-specific mortality, and overall mortality.
Chemoprevention involves medications to lower cancer risk. Selective estrogen receptor modulators (SERMs) such as tamoxifen or raloxifene can reduce breast cancer risk. Tamoxifen, for instance, may offer a breast cancer risk reduction of about 48% for high-risk individuals. These options are discussed with healthcare providers to create a personalized risk management plan.