Lynch syndrome (Hereditary nonpolyposis Colorectal Cancer: HNPCC) is a hereditary type of cancer that affects the colon and rectum. Patients with this syndrome have an increased risk of developing other types of cancers such as stomach, small intestine, liver, biliary tract, urinary tract, brain, skin and prostate cancer. Women with this syndrome have also higher risk of developing endometrial and ovarian cancer.
The genes whose mutations have been implicated in this syndrome are in descending frequency: MLH1 (involved in 50% of cases), MSH2 (40%), MSH6 (10%), and PMS2 (2%). These four genes (MLH1, MSH2, MSH6 and PMS2) are part of a group of genes called MMR (MistMatch Repair) genes, involved in the repair of DNA replication errors that occur during cell division. Mutations in any of these genes prevent proper error repair, so the cells accumulate errors in its DNA, eventually leading to uncontrolled growth and possibly cancer. The presence of mutations in these genes implies a greater risk, but not necessarily, to develop this syndrome and other cancers involved. These genes show an autosomal dominant inheritance, so the presence of a single altered copy in each cell is sufficient to increase the risk of developing this pathology.