Hereditary nonpolyposis colorectal cancer (HNPCC) may affect up to one out of 400 individuals in the western world and is characterized by a marked increase in colorectal carcinoma (CRC) susceptibility. CRCs occurring in HNPCC differ from sporadic CRCs in early age of onset, frequent proximal colon localization and excess of synchronous and metachronous lesions; extracolonic tumors are also associated. The predisposition to the disease is inherited in an autosomal dominant manner. Recently, patients from some HNPCC families have been shown to carry germline alterations in a group of genes named mismatch repair (MMR) genes, which codify for proteins involved in repairing DNA replication errors (hMSH2, hMLH1, hPMS1 and hPMS2). A pathogenic role has been proposed for these genes in causing hypermutability in cells of certain organs and tissues, such as colonic mucosa. They may facilitate activation of proto-oncogenes and inactivation of tumor suppressor genes involved in oncogenesis. MMR genes isolation has improved the characterization of the HNPCC syndrome. The identification of at least some genetic causes or predisposing factors allows a better characterization of the pathogenic mechanisms of HNPCC-associated neoplasias. Moreover, the use of MMR genes as molecular markers enables the genetic counsellor to recognize in an HNPCC family those members who are at risk, with important implications in clinical surveillance.
|Number of pages||8|
|Journal||Rivista Medica del Friuli|
|Publication status||Published - 1997|
ASJC Scopus subject areas