In Lynch syndrome (hereditary non-polyposis colorectal cancer), a pathogenic germline mutation in which gene creates a DNA mismatch repair deficiency and confers the highest lifetime risk of colorectal cancer?
- A MSH6
- B PMS2
- C MLH1 ✓
- D EPCAM
Correct answer: C. MLH1
Explanation
MLH1 and MSH2 mutations in Lynch syndrome carry the highest lifetime CRC risk (~70–80%), and MLH1 mutations are the most common cause of Lynch syndrome overall. MSH6 and PMS2 mutations confer lower penetrance CRC risk (~30–40% lifetime). EPCAM deletions inactivate MSH2 epigenetically and represent a less common cause. The Amsterdam II criteria and Bethesda guidelines are used to identify patients requiring germline testing.
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.