Clinical heterogeneity offamilial colorectal cancer anditsinfluence on screening protocols

Theageatonsetofnon-polyposis colorectalcancer(CRC)wasinvestigated in49 families withat leastthreerelatives affected intwosuccessive generations. Fortyoneofthesefamilies satisfy the accepted minimumcriteria forhereditary non-polyposis CRC.Theremaining eight families weredistinguished byalateageof disease onsetand,hence,couldnotbe included inthegroup.Thecondition in theselatter families hasbeendesignated provisionally, as lateonsetfamilial CRC.Thehereditary non-polyposis CRC families include 194patients, 110men and 84 women (meanageatdiagnosis: 44 years; range:16-74years). Ninety twoper centofthepatients werediagnosed byage 60.Colorectal cancerwas diagnosed at progressively earlier agesinsuccessive generations (p<0.0005). The lateonset CRC families comprised 30patients, 20 men and10women (meanageatdiagnosis: 62years; range:51-77years). Fifty eight percentoftheCRCsinthepatients belonging tothehereditary non-polyposis CRC families werelocated intheright coloncompared with13%inthelate onset familial CRC group(p<0.00l). Multiple CRCs werefoundin23%ofthecasesin theformerbutinonly3% inthelatter families (p<0.05). Adenomasassociated withCRC werereported in14.5%ofthe casesin thehereditary non-polyposis CRC families andin30% ofthecases in thelateonsetfamilial CRC group (p=NS). Extracolonic cancers, frequently encountered inhereditary non-polyposis