COLORECTAL NEOPLASMS DETECTED COLONOSCOPICALLY IN AT-RISK MEMBERS OF COLORECTAL-CANCER FAMILIES STRATIFIED BY THE DEMONSTRATION OF DNA MICROSATELLITE INSTABILITY

This study compared colonoscopic findings in families meeting the Amst erdam criteria (A) for hereditary non-polyposis colorectal cancer (HNP CC) but stratified according to whether the familial cancers showed DN A microsatellite instability, DNA was extracted from paired samples of normal and cancer, and microsatellite instability was analysed at up to six loci. Families were termed replication error positive (RER(+)) when at least 50% of tumours tested per family were positive. Of 26 fa milies studied 17 were RER(+) and 9 were RER(-). Cancers in the A/RER( -) families showed no right-sided predilection (P<0.001), Colonoscopie s have been performed on 182 at-risk members of A/RER(+) families and 60 members of A/RER(-) families. More of the at-risk members of A/RER( -) families were found to have adenomas at colonoscopy (P=0.095), but these were smaller than those of A/RER(+) families (P=0.19). The adeno ma:carcinoma ratio was twice as high in A/RER(-) families (13:1) as in A/RER(+) families (7:1). One of the A/RER(-) families had hyperplasti c polyposis. The others do not appear to have attenuated familial aden omatous polyposis and are similar to the adenoma families or late-onse t colorectal cancer families described by others. This study illustrat es the importance of molecular technology in separating HNPCC from syn dromes with overlapping phenotypes.