Regarding Lynch syndrome (HNPCC) colorectal cancer screening, which mismatch repair gene mutation is associated with the highest penetrance of colorectal cancer?

• A MSH6 — associated with 50-80% lifetime CRC risk
• B PMS2 — associated with 50-80% lifetime CRC risk
• C MLH1 and MSH2 — each associated with 50-80% lifetime CRC risk ✓
• D EPCAM deletion — associated with >80% CRC risk

Explanation

MLH1 and MSH2 mutations carry the highest penetrance in Lynch syndrome, with lifetime colorectal cancer risks of 50-80%. MSH6 mutations confer lower CRC risk (25-60%) but higher endometrial cancer risk. PMS2 mutations carry the lowest CRC penetrance (~15-20%). EPCAM deletions cause epigenetic silencing of MSH2 but do not themselves carry a higher risk than MSH2 mutation. Colonoscopic surveillance every 1-2 years beginning at age 20-25 is recommended for MLH1/MSH2 carriers.

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.