Makindo Medical Notes

BRCA gene mutations increase the risk of developing certain cancers, but they do not guarantee that a person will develop cancer. These mutations impair the body's ability to repair DNA damage, leading to a higher likelihood of genetic mutations that may result in malignancies.

About

• An estimated 5-10% of breast cancers are caused by inherited genetic mutations.
• The inheritance of BRCA mutations follows an autosomal dominant pattern, meaning that inheriting one copy of the mutated gene from either parent increases the risk of developing cancer.
• BRCA1 and BRCA2 are tumour suppressor genes involved in DNA repair . Mutations in these genes can impair the repair of damaged DNA, leading to the accumulation of further genetic errors that may result in cancer.
• Individuals with mutations in these genes have a significantly increased risk of developing breast and ovarian cancer.
• BRCA1 mutations: Associated with an increased risk of breast, ovarian, and pancreatic cancer.
• BRCA2 mutations: Associated with an increased risk of breast, ovarian, pancreatic, prostate cancer, and melanoma.
• Individuals with BRCA mutations may choose risk-reducing surgeries such as bilateral mastectomy (removal of both breasts) and oophorectomy (removal of ovaries) to lower the risk of developing cancer.

Inheritance and Risk

• Autosomal Dominant: Only one copy of a mutated BRCA1 or BRCA2 gene from either parent is needed to increase cancer risk.
• A person with a BRCA mutation has a 50% chance of passing the mutation on to their children.
• Not everyone with a BRCA mutation will develop cancer, but the risk is significantly higher compared to the general population.
• In women, the lifetime risk of breast cancer with a BRCA mutation can be as high as 60-80% , and the risk of ovarian cancer can be as high as 15-45% .
• Men with BRCA2 mutations have a higher risk of prostate cancer, with up to a 20% lifetime risk .

Associated Cancers

• Breast Cancer: The most common malignancy associated with BRCA1 and BRCA2 mutations, affecting both men and women.
• Ovarian Cancer: A major risk for women with BRCA mutations, often detected at later stages.
• Pancreatic Cancer: Both BRCA1 and BRCA2 mutations increase the risk of pancreatic cancer.
• Prostate Cancer: Men with BRCA2 mutations are at a higher risk of developing prostate cancer.
• Melanoma: BRCA2 mutations are also linked to an increased risk of melanoma (skin cancer).

Genetic Testing and Screening

• Genetic Testing: Individuals with a family history of breast, ovarian, or related cancers may be offered genetic testing to identify BRCA mutations.
• Screening: Individuals with BRCA mutations may undergo enhanced cancer screening, including earlier and more frequent mammograms, breast MRIs, and other imaging tests.
• Prophylactic Surgeries: Some individuals opt for preventive surgeries such as mastectomy or oophorectomy to significantly reduce their risk of developing cancer.

Management and Prevention

• Risk-Reducing Surgery: Bilateral mastectomy and salpingo-oophorectomy (removal of the fallopian tubes and ovaries) are options for high-risk individuals to reduce cancer risk.
• Medication: Drugs such as tamoxifen or raloxifene may reduce breast cancer risk in women with BRCA mutations.
• Lifestyle Modifications: Maintaining a healthy weight, reducing alcohol consumption, and regular physical activity may help reduce cancer risk.
• Family Planning: Preimplantation genetic diagnosis (PGD) is available for couples with BRCA mutations to ensure that embryos without mutations are implanted during in vitro fertilization (IVF).

Emotional and Psychological Considerations

• Testing positive for a BRCA mutation can lead to anxiety and emotional distress, as it involves decision-making about preventive surgeries and family planning.
• Counseling and support groups are available to help individuals and families cope with the implications of a BRCA mutation.