Hereditary nonpolyposis colorectal cancer

Hereditary nonpolyposis colorectal cancer (HNPCC), or Lynch syndrome, is the most common form of hereditary colorectal cancer (CRC). A well-orchestrated cancer family history is essential for its diagnosis since, unlike its familial adenomatous polyposis (FAP) hereditary cancer counterpart, HNPCC lacks distinguishing clinical stigmata of its cancer genetic risk. Discoveries in the 1990s of germ-line mutations, the most common of which are hMSH2 and hMLH1, have added enormous power to the diagnosis of Lynch syndrome. Its medical management is contingent upon its natural history. For example, approximate to 70% of CRCs occur proximal to the splenic flexure, with one-third of the cancers occurring in the cecum, thereby mandating full colonoscopy. A high rate of metachronous CRCs indicates the need for no less than a subtotal colectomy for the management of initial CRC. Genetic counseling is essential prior to DNA testing, and at the time of disclosure of the results. Education of patients as well as physicians about all facets of this disorder is extremely important. If patients are to show compliance with germ-line testing, screening, and management options, they must understand the natural history and the significance of their genetic risk status. Physicians must also be aware of clinical nuances of this disorder to provide the necessary care. Semin, Surg, Oncol. 18:305-313, 2000, (C) 2000 Wiley-Liss, Inc.