Radiation Oncology/Cancer Syndromes/HNPCC

Hereditary nonpolyposis colorectal cancer (HNPCC)

• wikipedia entry
• DNA Repair chapter

• Defect in DNA mismatch repair pathway (MLH1, MSH2, MSH6, PMS, PMS2)
• Microsatellite instability is a hallmark feature.
• Estimated to be responsible for ~5% of colorectal cancer; conversely, patients with HNPCC have ~80% risk of colon cancer and 30-50% risk of endometrial cancer.
• Also increased risk for ovarian, gastric, small intestine, hepatobiliary, upper urinary, brain, and skin
• Autosomal dominant, but has incomplete penetrance
• Criteria - Amsterdam criteria (PMID 2022152), Bethesda guidelines (PMID 9392616, Full text), PREMM_1,2 model (Prediction of Mutations in MLH1 and MSH2)
  • 3 colon cancers in which 2 people are first-degree relatives of the third. Cancer in 2 generations. One diagnosis before age 50. No evidence of FAP
  • However, up to 40% of families with these mutations don't meet the Amsterdam criteria.
• Average age of developing cancer: 45 years (vs 63)
• Screening: full colonoscopy q3y beginning age 20-25; annual endometrial screening age 25-35