Which mutation is most strongly associated with hereditary epithelial ovarian cancer and increases lifetime risk to approximately 40–60%?

• A TP53 germline mutation (Li-Fraumeni syndrome)
• B BRCA1 germline pathogenic variant ✓
• C MLH1 germline mutation (Lynch syndrome)
• D PTEN germline mutation (Cowden syndrome)

Explanation

BRCA1 germline pathogenic variants confer a lifetime ovarian cancer risk of approximately 40–60%, while BRCA2 variants confer a 15–25% risk. Lynch syndrome (MLH1, MSH2, MSH6, PMS2) is associated primarily with endometrial and colorectal cancer but also carries a 6–12% ovarian cancer risk. PTEN mutations predispose to endometrial cancer. TP53 mutations in Li-Fraumeni syndrome cause sarcomas and other tumours.

Reference: Shaw's Textbook of Gynaecology, 17th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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