Hereditary nonpolyposis colorectal cancer (HNPCC) is the most frequent form of hereditary colorectal cancer. Its diagnosis is based on the presence of three criteria, defined in 1991 in Amsterdam, and revised in 1999: i) at least three subjects with histologically proven cancers belonging to the narrow spectrum of the HNPCC syndrome (hereditary predisposition to colorectal and endometrial adenocarcinomas), ii) paired with a first-degree family relationship over at least two generations and iii) at least one of the cancers diagnosed before the age of 50 years. In the families identified based on these criteria, the affected subjects primarily develop colorectal, with or without endometrial cancers, with a cumulative risk of 70-80% at 70 years. The disease is transmitted as an autosomal dominant trait. The gene(s) associated with the HNPCC syndrome belong to the family of DNA mismatch repair (MMR) genes involved in the control of replication. Mutations in the MSH2 (MutS homolog 2, 16 exons), MLH1 (MutL homolog 1, 19 exons) and MSH6 (2p16, 10 exons) genes have been detected in respectively, 35, 25 and 2% of the cases. No genetic mutation has been found in about a third of the patients. Monitoring by colonoscopy is recommended every 2 years, as of 20 years of age, for individuals carrying a constitutional mutation in the MSH2, MLH1 or MSH6 gene. Gynecological monitoring of women over 30 years old is also recommended. The treatment of these cancers is the same as that given in the absence of any predisposition. No preventive treatment exists.
Last update: December 2004