Our bodies are built and maintained by a complex set of instructions found within our genes. These genes provide the blueprint for everything from eye color to how our cells grow and divide. One of these, known as BRCA2, plays a significant part in maintaining cellular health. Located on the long arm of chromosome 13, the BRCA2 gene has been a focus of scientific research because of its connection to cell stability and its role when that stability is compromised.
Function of the BRCA2 Gene
Every person has two copies of the BRCA2 gene, one inherited from each parent. Its primary role is to function as a tumor suppressor. The protein produced by this gene is a component of the cell’s DNA repair machinery, acting to protect our genetic information. It is expressed in various tissues, including the breast and ovaries, where it helps to mend damage to our DNA from environmental exposures or as a natural part of cell processes.
The BRCA2 protein is important for a repair process called homologous recombination. When a dangerous double-strand break occurs in DNA, the BRCA2 protein helps recruit other repair proteins, such as RAD51, to the site of the break. This response ensures the DNA is repaired accurately, preventing the loss of genetic information and maintaining the stability of a cell’s genome.
This repair function also ensures stability during cell division. As cells replicate, their DNA is vulnerable to errors, and the BRCA2 protein helps protect the DNA replication forks from degrading. This protective role prevents the accumulation of genetic mistakes that could otherwise lead to uncontrolled cell growth, safeguarding cells from becoming cancerous.
Health Risks of BRCA2 Mutations
When a person inherits a harmful variant, or mutation, in one copy of their BRCA2 gene, its ability to repair DNA is impaired. This doesn’t mean cancer will automatically develop, but their lifetime risk for certain cancers increases significantly. The single functioning copy of the gene is sufficient to suppress tumor development for some time. However, if that second copy becomes damaged in a cell, it can lead to cancer.
The most well-known risks associated with BRCA2 mutations are for breast and ovarian cancer. Women with a harmful BRCA2 mutation have a lifetime risk of developing breast cancer that can be as high as 85%, compared to about 13% in the general population. Their risk of ovarian cancer is also elevated, at up to 27%. These mutations can be passed down from either the mother or the father, a fact sometimes overlooked in family health history.
The cancer risks are not limited to women. Men with BRCA2 mutations also face an increased risk of breast cancer, which is much rarer in the general male population. These mutations also elevate the lifetime risk for prostate cancer, often leading to an earlier diagnosis and a more aggressive form of the disease. Both men and women with BRCA2 mutations have a higher risk of developing pancreatic cancer and melanoma.
The loss of the gene’s function connects these different cancers. A faulty BRCA2 protein cannot effectively mend DNA breaks, allowing genetic errors to accumulate across tissues. This genomic instability is a common feature of tumors that develop in individuals with these mutations. Environmental and other genetic factors may play a role in why certain organs are more susceptible.
Genetic Testing and Interpretation
Genetic testing can determine an individual’s BRCA2 status and is recommended for those with a significant personal or family history of related cancers. Considerations for testing include:
- Breast cancer diagnosis at a young age (under 50)
- A diagnosis of triple-negative breast cancer or male breast cancer
- A family history with multiple relatives having breast, ovarian, prostate, or pancreatic cancer
- Being of Ashkenazi Jewish descent, due to a higher prevalence of mutations
The testing process involves a blood or saliva sample, from which DNA is extracted and the BRCA2 gene is analyzed. The results are categorized into three possibilities. A “positive” result means a known harmful, or pathogenic, mutation was found, confirming an increased cancer risk. A “negative” result indicates that no such mutation was identified.
A third result is a “Variant of Uncertain Significance” (VUS). This means a change was detected in the BRCA2 gene, but it is not yet known if that specific variant affects protein function or increases cancer risk. A VUS result does not provide a clear answer, so medical management is often based on family history until more definitive information becomes available. Genetic counseling helps individuals understand their results and the implications for their health and family.
Management and Risk Reduction Strategies
Receiving a positive result for a BRCA2 mutation allows individuals to take proactive steps to manage their cancer risks. Management strategies are personalized and involve a combination of enhanced surveillance, risk-reducing medications, and preventive surgeries. The goal is to detect cancer at its earliest stage or to lower the risk of it developing.
Enhanced surveillance means starting cancer screenings at an earlier age and having them more frequently. For women, this may include annual mammograms and breast MRIs, often beginning as early as age 25. Screenings for ovarian cancer, such as transvaginal ultrasounds and blood tests, may also be recommended. A comprehensive plan also includes discussions about screening for prostate cancer, pancreatic cancer, and melanoma.
Certain medications can help lower cancer risk. For example, drugs like tamoxifen or aromatase inhibitors, which block the effects of estrogen, can reduce the risk of developing certain types of breast cancer in women. These medications, known as chemoprevention, are a consideration for those who have not had cancer or to prevent a new cancer.
For the greatest risk reduction, prophylactic, or risk-reducing, surgeries are an option. A prophylactic mastectomy involves removing healthy breast tissue to lower the risk of breast cancer. Similarly, a risk-reducing salpingo-oophorectomy, the removal of the ovaries and fallopian tubes, decreases the risk of both ovarian and breast cancer. These are major decisions with physical and emotional impacts, made in consultation with a healthcare team.