Lynch Syndrome

Lynch syndrome (LS) is the most common form of hereditary colorectal cancer (CRC), and previously it was called hereditary non-polyposis colorectal cancer (HNPCC). LS is an inherited tumor predisposing condition caused by mutations in the DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6 or PMS2) or in the EPCAM gene, which inactivates MSH2 via promoter hypermethylation. The proteins produced by MLH1, MSH2, MSH6 and PMS2 form heterodimeric complexes, which play an essential role in DNA repair. Genotype–phenotype correlations are established because cancer risk depends on the mutated MMR gene. The genotype deficient in MMR genes (MMR deficient) is associated with a lifetime cancer risk of 58–75% with frequent observations of the development of synchronous/metachronous tumors. Lynch-associated CRCs behave differently than sporadic CRCs, which has significant implications for clinical management. Histopathological examination of Lynch-associated CRCs often reveals abundant lymphocytes infiltrating the tumor.