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.