Surveillance on mutation carriers of DNA mismatch repair genes

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant inherited cancer susceptibility syndrome signifying a very high risk of colorectal and endometrial cancer at young age. It also entails an increased risk of a variety of other tumours, such as ovarian, gastric, uroepithelial and biliary tract cancer. The underlying pathogenic mutation lies in one of the five known DNA mismatch repair genes (MSH2, MLH1, PMS1, PMS2, and MSH2). The majority of HNPCC patients and families can at present be identified and the underlying mutation detected by genetic diagnostics. This provides the opportunity for predictive genetic testing to exclude or identify the mutation carrier status of the family members at risk. Mutation-negative individuals can then be relieved from any extra cancer threat. For mutation-positive individuals a preventive surveillance programme offers substantial benefits in reducing the cancer incidence, almost precluding death of colorectal cancer and reducing overall mortality.