In Lynch syndrome (HNPCC), which mismatch repair (MMR) gene mutation is associated with the HIGHEST cumulative lifetime risk of colorectal cancer?
- A MLH1 mutations ✓
- B MSH6 mutations
- C PMS2 mutations
- D EPCAM deletions
Correct answer: A. MLH1 mutations
Explanation
MLH1 mutations confer the highest cumulative lifetime risk of colorectal cancer in Lynch syndrome, approximately 40–80%, followed by MSH2 (~40–70%), MSH6 (~10–22%), and PMS2 (~15–20%). EPCAM deletions cause MSH2 epigenetic silencing and carry risk comparable to MSH2. MSH6 mutations are more strongly associated with endometrial cancer than CRC. PMS2 is the lowest-penetrance MMR gene for CRC. The Amsterdam II criteria and surveillance intervals are adjusted based on gene involved.
Reference: Bailey & Love's Short Practice of Surgery, 27th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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