Lynch syndrome (LS) is the most common cause of hereditary colorectal cancer (CRC), resulting from a germline pathogenic variant in one of the DNA mismatch repair (MMR) genes.  The MMR genes associated with LS include MSH2, MLH1, MSH6 and PMS2.

The role of the MMR system is to correct base substitution mismatches and small insertions and deletions that occur during DNA replication.  Inactivation of both copies of any of the MMR genes can lead to ineffective mismatch repair which will result in an increased mutation rate in the cell (genomic instability), resulting in carcinogenesis.

Mismatch repair, microsatellite instability and germline testing in Lynch Syndrome