Genetic epidemiology of mutated K-ras proto-oncogene, altered suppressor genes, and microsatellite instability in colorectal adenomas

Background-The genetic epidemiology of colorectal adenomas has not been stu died prospectively in colonoscopy patients without cancer. Aims-To study genetic alterations in colorectal adenomas and correlate thes e with patient demographics and adenoma characteristics. Methods-Mutations and allelic deletions in 201 adenomas from 60 patients we re compared with demographic features, adenoma characteristics, and family history. Results-The most common alteration was K-ras proto-oncogene mutation, prese nt in 35% of adenomas and 65% of patients. Patients 65 years of age and old er had a decreased probability of K-ras mutations (26% versus 45%). Overexp ression of p53 gene product was present in only 6% of adenomas but was more frequent in villous or tubulovillous adenomas (19% versus 3%). Allelic los s of chromosome 18q was present in only 2% of adenomas and was significantl y less frequent than p53 overexpression. DNA replication errors (RER) were present in 7% of adenomas and 15% of patients, including multiple adenomas in four patients (two with hereditary non-polyposis colorectal cancer syndr ome). Only 36% of RER positive adenomas had alteration of BAT-26 alleles, n one had alteration of BAT-25, and only one (8%) had mutation in the transfo rming growth factor beta type II receptor gene. RER positive adenomas were more likely to have a K-ras mutation. In patients with multiple adenomas, t here was concordance of p53 overexpression and RER but not of K-ras mutatio ns. Conclusions-Genetic progression in colorectal adenomas is heterogeneous, in volving factors related to patient age and the presence of RER for the occu rrence of ras mutations, but different intraindividual characteristics for the occurrence of p53 alterations and RER.