Lynch syndrome or hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disorder that is associated with a high risk of developing colorectal, stomach, endometrial, and several other types of cancers. HNPCC accounts for about 1% of colorectal cancers, and its prevalence is estimated to be 1:3000. Some populations, e.g. Finns, show a founder effect. Despite the availability of genetic tests for Lynch syndrome, family history remains the most important tool for the diagnosis of this disease.
HNPCC is defined by variations in genes that encodes components of the DNA mismatch repair (MMR) system. Mutations in these genes lead to failure of the repair mechanism and the errors introduced into DNA during DNA replication gets accumulated over time resulting in cells with very high rates of somatic mutation. These cellular events may prompt the inactivation of tumor suppressor genes or activation of cellular oncogenes, thereby, triggering cancer development. To date, mutations in four genes - MSH2, MLH1, PMS2, and MSH6, all of which encodes components of the mismatch repair pathway have been shown to increase the risk of developing Lynch syndrome. MSH2 and MLH1 variations account for approximately 90% of HNPCC and service provision is generally based on analysis of these two genes. Mutations in EPCAM gene involved in MSH2 gene regulation have also been known to cause Lynch syndrome.