BRCA1 is a gene found in humans. The name “BRCA” is an abbreviation for “BReast CAncer gene,” with “1” indicating it was the first of these genes identified. This gene is a component of human DNA and plays a role in maintaining overall health. Everyone possesses two copies of the BRCA1 gene, inheriting one from each parent.
The Normal Role of BRCA1
The BRCA1 gene provides instructions for creating a protein that functions as a tumor suppressor. This protein helps regulate cell growth and division, preventing them from multiplying too rapidly or uncontrollably. The BRCA1 protein is involved in repairing damaged DNA within the cell’s nucleus.
DNA can incur damage from various sources, including natural processes, medical radiation, or environmental exposures. The BRCA1 protein interacts with other proteins to mend breaks in DNA, such as double-strand breaks. This repair process helps maintain the stability of a cell’s genetic information. The BRCA1 protein also acts as a checkpoint regulator in the cell cycle, pausing cell division when DNA damage is detected to allow for repairs. If the damage is too extensive, it can even trigger programmed cell death to eliminate potentially dangerous cells.
BRCA1 Mutations and Cancer Risk
A mutation in the BRCA1 gene signifies an alteration that prevents it from functioning correctly, often leading to a shortened, non-functional protein or no protein at all. With a non-functional BRCA1 protein, the cell’s ability to repair damaged DNA is compromised, allowing defects to accumulate. These accumulating defects can then trigger cells to grow and divide without order, potentially forming a tumor. While a BRCA1 mutation does not guarantee cancer, it significantly increases an individual’s lifetime risk for developing certain cancers.
These mutations are inherited and can be passed down from either parent to their children. Cancers linked to BRCA1 mutations often appear to cluster within families. Women with a harmful BRCA1 mutation face a substantially elevated lifetime risk of breast cancer, with estimates ranging from 60% to 75% by age 70. They also have a significantly increased risk of ovarian cancer, with estimates between 39% and 58% over a lifetime, encompassing fallopian tube and primary peritoneal cancers. Breast cancers associated with BRCA1 mutations are often triple-negative, a subtype that lacks estrogen receptors, progesterone receptors, and HER2/neu protein, making them more challenging to treat.
BRCA1 mutations also increase the risk for other cancers. Men carrying a BRCA1 mutation have a higher risk of prostate cancer, and both men and women are at an increased risk for pancreatic cancer. There is also an association with male breast cancer. The risk of developing a second primary breast cancer is also elevated for those who have already had breast cancer and carry a BRCA1 mutation, with about 30% to 40% developing a contralateral breast cancer within 20 years.
Genetic Testing and Management
Genetic testing for BRCA1 mutations is typically considered for individuals with a strong personal or family history of breast, ovarian, fallopian tube, or peritoneal cancer, or those diagnosed with certain cancers at a younger age. This also includes individuals with Ashkenazi Jewish heritage due to a higher prevalence of specific BRCA1 mutations in this population. The testing process usually involves providing a blood or saliva sample.
A positive test result indicates the presence of a harmful BRCA1 mutation and an increased risk of developing certain cancers; it does not mean cancer is present. Following a positive result, genetic counseling is recommended to understand the implications for the individual and their family. Risk management strategies are then discussed, which may include increased surveillance. For example, women with BRCA1 mutations are often advised to begin annual breast MRI and mammography between ages 30 and 75. Men with BRCA1 mutations may also consider earlier prostate cancer screening.
Risk-reducing surgeries are another option. These include prophylactic mastectomy and prophylactic oophorectomy. Chemoprevention can also be considered. Ultimately, the choice of management plan is personalized, taking into account individual risk factors, family history, and personal preferences, with guidance from healthcare professionals.