FREQUENCY OF REPLICATION ERRORS IN COLORECTAL-CANCER AND THEIR ASSOCIATION WITH FAMILY HISTORY

Background-Replication errors (RERs) characterise tumours of hereditar y nonpolyposis colorectal cancer (HNPCC). RER status may therefore imp rove identification of such families previously diagnosed by family hi story alone. Aims-To assess RER and HNPCC frequency within a populatio n of colorectal cancer patients and a regional population of family hi story defined (Amsterdam criteria) HNPCC families. Methods-Family hist ory was assessed by personal interview in a population of 479 patients with colorectal cancer attending one follow up clinic. Seven fluoresc ently labelled microsatellites were used to investigate RER frequency in colorectal cancers from 89 patients of this population with varying degrees of family history and 20 Amsterdam criteria positive families (four with a known germline mutation, 16 with unknown mutation status ) from the regional population. Results-Only four of the follow up pop ulation (0.8%) came from families meeting the Amsterdam criteria with only one showing RERs. The frequency of RERs was similar in the early onset cancer group (less than 50 years of age), those with a family hi story,:and those with no family history of colorectal cancer. From the regional population, RERs were identified in 4/4 families with a muta tion but only 8/16 families with unknown mutation status. Conclusions- No correlation was seen between RER status and strength of family hist ory except in HNPCC families. Results also indicate that half of the A msterdam criteria defined families do not exhibit RERs, perhaps sugges ting a different mechanism of tumorigenesis.