Lynch syndrome (HNPCC) is associated with an increased lifetime risk of endometrial carcinoma. Which mismatch repair gene mutation carries the HIGHEST lifetime risk of endometrial cancer in Lynch syndrome?

• A MLH1
• B MSH2
• C PMS2
• D MSH6 ✓

Explanation

In Lynch syndrome, MSH6 mutations confer the highest lifetime risk of endometrial carcinoma (up to 71% by age 70), exceeding colorectal cancer risk in women with MSH6 mutations. MLH1 and MSH2 mutations carry approximately 40–60% endometrial cancer risk. PMS2 mutations carry lower cancer risks. This distinction is clinically important for counselling and surveillance recommendations (annual endometrial sampling and pelvic ultrasound from age 30–35).

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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