ABSTRACT
In colorectal tumorigenesis, Ki-ras proto-oncogene mutation often occurs early in the adenoma-adenocarcinoma sequence, whereas mutation of the p53 gene is associated with late progression to carcinoma. We evaluated the relationship of demographic and clinicopathologic characteristics to Ki-ras mutation and p53 gene product overexpression in 1,093 baseline sporadic colorectal adenomas from 926 individuals enrolled in a phase III recurrence prevention trial. Ki-ras mutation was found in 14.7% of individuals and p53 overexpression was found in 7.0% of those tested. Multivariate analysis found older age, rectal location, and villous histology to be independently associated with Ki-ras mutation. Individuals with an advanced adenoma (>or=1 cm or high-grade dysplasia or villous histology) had a 4-fold higher likelihood of Ki-ras mutation [odds ratios (OR), 3.96; 95% confidence intervals (CI), 2.54-6.18]. Ki-ras mutations in codon 12 and of the G-to-A transition type were more frequent in older individuals, whereas G-to-T transversion was more frequent in rectal adenomas than in the colon. Multivariate analysis showed that previous history of a polyp (P = 0.03) was inversely associated with p53 overexpression. Large adenoma size (>or=1 cm), high-grade dysplasia, and villous histology were independently associated with p53 overexpression, with the strongest association for advanced adenomas (OR, 7.20; 95% CI, 3.01-17.22). Individuals with a Ki-ras mutated adenoma were more likely to overexpress p53 (OR, 2.46; 95% CI, 1.36-4.46), and 94.8% of adenomas with both alterations were classified as advanced (P Subject(s)
Adenoma, Villous/genetics
, Colorectal Neoplasms/genetics
, Genes, p53/genetics
, Genes, ras/genetics
, Mutation
, Adenocarcinoma/genetics
, Adenocarcinoma/metabolism
, Adenocarcinoma/pathology
, Adenoma, Villous/metabolism
, Adenoma, Villous/pathology
, Adult
, Aged
, Aged, 80 and over
, Case-Control Studies
, Colorectal Neoplasms/metabolism
, Colorectal Neoplasms/pathology
, DNA Mutational Analysis
, Demography
, Female
, Humans
, Immunoenzyme Techniques
, Male
, Middle Aged
, Polymerase Chain Reaction
, Proto-Oncogene Mas