Lynch syndrome (Hereditary Non-Polyposis Colorectal Cancer — HNPCC) is the most common hereditary cause of endometrial cancer. Which mismatch repair gene mutation is associated with the highest risk of endometrial cancer in Lynch syndrome?

• A MLH1 mutation
• B PMS2 mutation
• C APC mutation
• D MSH6 mutation ✓

Explanation

In Lynch syndrome, MSH6 mutations confer the highest lifetime risk of endometrial cancer (approximately 65–71%), higher than the associated colorectal cancer risk in MSH6 carriers. MLH1 and MSH2 mutations are more commonly associated with colorectal cancer. PMS2 mutations have lower overall cancer risk. APC mutations cause familial adenomatous polyposis, not Lynch syndrome. Women with Lynch syndrome may develop endometrial cancer as their sentinel cancer, preceding colorectal cancer.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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