Lynch syndrome (hereditary non-polyposis colorectal cancer, HNPCC) is caused by germline mutations in mismatch repair (MMR) genes. Which gene mutation confers the highest lifetime risk of endometrial cancer, approaching 40-60%?
- A MSH6 ✓
- B MLH1
- C PMS2
- D MSH2
Correct answer: A. MSH6
Explanation
MSH6 mutations in Lynch syndrome are associated with a relatively lower colorectal cancer risk compared to MLH1/MSH2 but a disproportionately high endometrial cancer risk (40-60% lifetime), exceeding the colorectal cancer risk in affected women. MSH2 mutations confer the highest urinary tract cancer risk. Gynecological surveillance with annual endometrial sampling and consideration of prophylactic hysterectomy after childbearing is particularly important for female MSH6 mutation carriers.
Reference: Bailey & Love's Short Practice of Surgery, 27th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.