Klin Onkol 2006; 19(Suppl): 76-81.
Summary
Lynch syndrome hereditary nonpolyposis colorectal cancer (HNPCC) is the most frequent of known hereditary predispositions to colon cancer. It is responsible for approximately 2% of all colon cancers in the population. Patients with Lynch syndrome are at high lifelong risk of the colon cancer and some other malignancies. The main cause of Lynch syndrome is the germline mutation of one of the DNA mismatch repair (MMR) genes. Clinical suspicion of the Lynch syndrome is based mainly on concurrent colorectal cancer without familial adenomatous polyposis, colon cancer in relatives and manifestation before the age of 50 years. The diagnosis is supported by the presence of microsatellite instability in tumour DNA and by the loss of expression of MMR proteins in tumour tissue demonstrated by immunohistochemistry. The diagnosis of Lynch syndrome is confirmed at the molecular level by the detection of a pathogenic germline mutation in the MMR gene. Complex diagnostic procedures were suggested to improve the effectivity of diagnostic process. Detection of a pathogenic mutation in a patient enables a predictive testing in his/her relatives. Long term follow up of patients and their positively tested relatives improves their prognosis. Search for new candidate genes, optimisation of the diagnosis and follow up are the matter of current research.
