Lynch syndrome is caused by germline mutations in mismatch repair (MMR) genes. Which gene mutation is associated with the highest lifetime risk of colorectal cancer?
- A MLH1 ✓
- B MSH6
- C PMS2
- D MSH2
Correct answer: A. MLH1
Explanation
Germline mutations in MLH1 are associated with the highest cumulative lifetime risk of colorectal cancer among Lynch syndrome genes, approximately 52–82% by age 70. MLH1 and MSH2 mutations confer the highest overall cancer risks; MSH6 and PMS2 mutations carry lower penetrance with later-onset disease. MLH1 is also critical because its promoter hypermethylation causes the majority of sporadic MSI-H colorectal cancers, making it the most clinically relevant MMR gene.
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.