Problems in the identification of hereditary nonpolyposis colorectal cancer in two families with late development of full-blown clinical spectrum

The recognition of Hereditary Nonpolyposis Colorectal Cancer (HNPCC) remain s difficult despite the most recent advancements of molecular biology and t echnology. We describe two families with early onset of cancer but no suspi cion of hereditary tumors; during follow-up, both families developed a tumo r spectrum highly suggestive of HNPCC, thus emphasizing the importance of f amily history For a proper identification of hereditary tumors or cancer ag gregation. Microsatellite instability was negative in tumors from both fami lies and, as expected, no germline mutations of the major DNA mismatch repa ir genes (MSH2 and MLH1) could be detected. Suspicion of the disease at the time of proband's lesion might have led to prevention, or early diagnosis, of at least three malignant turners. We conclude that a possible genetic o rigin should always be suspected in individuals with early-onset neoplasms of the large bowel and probably of other organs such as the endometrium, sm all bowel, and urothelium, even when the initial pedigree does not show mar ked aggregation of cancers or vertical transmission. (C) 2000 by Am. Cell. of Gastroenterology.