The BRCA1 and BRCA2 mutations most commonly predispose to which histological subtype of ovarian cancer, and what is the lifetime risk of ovarian cancer in BRCA1 mutation carriers?
- A Mucinous carcinoma; lifetime risk ~10%
- B Endometrioid carcinoma; lifetime risk ~15–20%
- C High-grade serous carcinoma; lifetime risk ~40–50% ✓
- D Clear cell carcinoma; lifetime risk ~25–30%
Correct answer: C. High-grade serous carcinoma; lifetime risk ~40–50%
Explanation
BRCA1 and BRCA2 mutations predominantly predispose to high-grade serous carcinoma (HGSC), which accounts for ~70% of all ovarian cancer deaths. HGSC commonly arises from the fallopian tube fimbriae (serous tubal intraepithelial carcinoma — STIC) rather than the ovarian surface epithelium. The lifetime risk of ovarian cancer in BRCA1 carriers is approximately 40–50%, compared to 15–20% for BRCA2 carriers and <2% in the general population. Risk-reducing salpingo-oophorectomy is recommended after childbearing completion, typically at age 35–40 for BRCA1.
Reference: Shaw's Textbook of Gynaecology, 17th ed.
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