DISEASE EXPRESSION IN SWISS HEREDITARY NONPOLYPOSIS COLORECTAL-CANCER(HNPCC) KINDREDS

The genetics of Hereditary Non-Polyposis Colorectal Cancer (HNPCC) has recently been established and found to be associated with DNA mismatc h repair deficiency. As the molecular basis of this syndrome does not appear to predict any particular disease, we compared families selecte d according to the ''Amsterdam'' criteria (AC) against families that w ere selected because of an aggregation of colonic and extracolonic mal ignancies (EC), all of which have been observed in HNPCC families. A c omparison of the 2 groups revealed that there were significant differe nces between them. Age at disease onset for both groups was 20-30 year s younger than in the general population; however, a normal age distri bution was observed for the AC group whereas for the EC group a bimoda l distribution was apparent. The prognosis for both groups together di d not differ from that of the general population; however, if split, t he At group had a significantly better outcome than the EC group. Furt hermore, dividing the AC group into hMSH2- and hMLHI-linked families r evealed that there was no difference in severity of disease between th ese 2 groups with respect to survival and mean age of disease onset. B oth the AC and EC groups displayed a similar tumour spectrum with a vi rtually identical tumour distribution. A significant finding was the o verrepresentation, of brain tumours in this family set, which comprise d the third most common malignancy after endometrial and stomach cance r. (C) 1997 Wiley-Liss, Inc.