Makindo Medical Notes

🧬 BRCA gene mutations increase the risk of several cancers but do not guarantee their development. These mutations impair DNA repair, leading to accumulation of genetic errors and a higher likelihood of malignancy.

📖 About

• ☑️ Around 5–10% of breast cancers are caused by inherited mutations.
• 🧬 BRCA1 and BRCA2 are tumour suppressor genes involved in DNA repair.
• Inheritance is autosomal dominant – only one faulty copy is needed to raise cancer risk.
• BRCA mutations greatly increase the lifetime risk of breast and ovarian cancer, and also affect other sites.
• BRCA1: ↑ risk of breast, ovarian, and pancreatic cancers.
• BRCA2: ↑ risk of breast, ovarian, pancreatic, prostate cancer, and melanoma.
• Some people choose risk-reducing surgery (bilateral mastectomy, oophorectomy) to lower risk.

👪 Inheritance and Risk

• Autosomal Dominant: One copy of the mutated gene from either parent is sufficient.
• 📊 A carrier has a 50% chance of passing it on to children.
• 🎀 Women with BRCA mutations:
  • Breast cancer risk: 60–80%
  • Ovarian cancer risk: 15–45%
• 🧔 Men with BRCA2 mutations: ↑ prostate cancer risk (~20% lifetime).
• ➡️ Not everyone with BRCA mutations develops cancer, but risk is many times higher than general population.

🎯 Associated Cancers

• 🎀 Breast cancer – both men & women.
• 🥚 Ovarian cancer – especially in BRCA1 carriers, often late diagnosis.
• 🍐 Prostate cancer – more common in BRCA2 carriers.
• 🍎 Pancreatic cancer – risk increased with both BRCA1 and BRCA2.
• 🌞 Melanoma – linked to BRCA2 mutations.

🧪 Genetic Testing & Screening

• 🧾 Genetic testing offered to those with strong family history of breast/ovarian cancer.
• 🔍 Enhanced screening:
  • Earlier & more frequent mammograms
  • Breast MRI (higher sensitivity in younger women)
• 🩺 Prophylactic surgery – mastectomy, salpingo-oophorectomy significantly reduce risk.

⚕️ Management & Prevention

• 🔪 Risk-reducing surgery: Bilateral mastectomy, salpingo-oophorectomy.
• 💊 Medication: Tamoxifen or raloxifene may reduce breast cancer risk.
• 🏃 Lifestyle: Healthy weight, ↓ alcohol, physical activity may help reduce risk.
• 👶 Family planning: Preimplantation genetic diagnosis (PGD) with IVF can prevent passing mutations to children.

💭 Emotional & Psychological Impact

• 😟 Positive BRCA test → anxiety & difficult decisions about surgery, surveillance, and family planning.
• 💬 Genetic counselling is essential before and after testing.
• 🤝 Support groups provide psychological support and shared experiences.

💡 Exam Pearls

• 🔑 BRCA mutations = autosomal dominant tumour suppressor gene defect.
• 🎀 Key association = early-onset breast & ovarian cancers.
• 📊 NICE: women with BRCA should be offered MRI screening from age 30.
• 👨 Men with BRCA2 mutation – think prostate cancer risk.