CLINICAL HETEROGENEITY OF FAMILIAL COLORECTAL-CANCER AND ITS INFLUENCE ON SCREENING PROTOCOLS

The age at onset of non-polyposis colorectal cancer (CRC) was investig ated in 49 families with at least three relatives affected in two succ essive generations. Forty one of these families satisfy the accepted m inimum criteria for hereditary non-polyposis CRC. The remaining eight families were distinguished by a late age of disease onset and, hence, could not be included in the group. The condition in these latter fam ilies has been designated provisionally, as late onset familial CRC. T he hereditary non-polyposis CRC families include 194 patients, 110 men and 84 women (mean age at diagnosis: 44 years; range: 16-74 years). N inety two per cent of the patients were diagnosed by age 60. Colorecta l cancer was diagnosed at progressively earlier ages in successive gen erations (p<0.0005). The late onset CRC families comprised 30 patients , 20 men and 10 women (mean age at diagnosis: 62 years; range: 51-77 y ears). Fifty eight per cent of the CRCs in the patients belonging to t he hereditary non-polyposis CRC families were located in the right col on compared with 13% in the late onset familial CRC group (p<0.001). M ultiple CRCs were found in 23% of the cases in the former but in only 3% in the latter families (p<0.05). Adenomas associated with CRC were reported in 14.5% of the cases in the hereditary non-polyposis CRC fam ilies and in 30% of the cases in the late onset familial CRC group (p= NS). Extracolonic cancers, frequently encountered in hereditary non-po lyposis CRC, were not found in the late onset CRC families. These find ings indicate that there is a distinct clinical entity of non-polyposi s CRC in which colorectal cancer develops at a more advanced age than in hereditary non-polyposis CRC. Future molecular genetic studies shou ld confirm this hypothesis. In the meantime, recognition of these late onset familial CRC families, which will rest on clinical observations , is important because of the implications for the screening protocol.