Hereditary non-polyposis colorectal cancer (HNPCC). Review on etiology, clinic, diagnosis and therapy

Etiology: The hereditary non-polyposis colorectal carcinoma (HNPCC) is the most common monogenic colon cancer syndrome. It is characterized by autosom al dominant inherited cancers of the colon, rectum, and the endometrium. Le ss frequently, cancer of the upper gastrointestinal tract, the hepatobiliar y system and the urogenital tract may occur. Typical characteristics are an early onset, usually before the age of 50, manifestation of colorectal can cer proximal of the splenic flexure, and often poorly differentiated carcin omas. Genetics: Recently, germline mutations in several DNA mismatch repair genes have been identified as the molecular basis of HNPCC, resulting in deficie nt DNA repair and genetic instability, indicated by microsatellite instabil ity in tumor specimens. Diagnosis: New insights into pathogenesis, clinical features, and diagnosis of HNPCC have improved the identification of HNPCC patients and persons at risk. Diagnosis of HNPCC is primarily based on family history and is compl emented by molecular findings. After detection of the underlying germline m utation in families with HNPCC, screening procedures can be restricted to m utation carriers. Treatment: Recommendations for therapy and prevention are in part controver sial and are under investigation in several studies.