K‐ras mutations in incident sporadic colorectal adenomas

BACKGROUND Although K‐ras is the most frequently mutated protooncogene in colorectal carcinoma, the specific role and timing of K‐ras mutations in colorectal carcinogenesis remains controversial. In the current study, the authors investigated associations with K‐ras mutation in incident sporadic colorectal adenomas that occurred during a chemoprevention trial of calcium supplementation. METHODS K‐ras genotyping was performed on 303 colorectal adenomas that were removed from 207 participants during the follow‐up phase of the Calcium Polyp Prevention Study. Mutations in codons 12 or 13 of K‐ras were detected by denaturing high‐performance liquid chromatography and were confirmed by direct sequencing. RESULTS The adenomas analyzed had a mean estimated size of 0.5 cm, and 3.0% were identified with mutations (95% confidence interval [95% CI], 1.3–4.4%). These mutations were more common in larger adenomas (risk ratio [RR], 12.7 for tumors that measured > 0.5 cm vs. ≤ 0.5 cm; 95% CI, 2.7–59.7), in adenomas with more advanced histology (RR, 20.6 for tubulovillous/villous vs. tubular; 95% CI, 4.4–96.0), and in adenomas that were located in the rectum compared with the colon (RR, 8.4; 95% CI, 2.3–30.5). CONCLUSIONS Compared with previous studies, the current analysis was novel, because it focused on incident adenomas that were diagnosed within a few years of a previous “clean” colonoscopy. The results provided evidence for a very low rate of K‐ras mutation among these small, early adenomas and strong support for a role of K‐ras mutations in adenoma progression. Cancer 2006. © 2006 American Cancer Society. K‐ras mutations were found in only 3.0% of 303 sporadic colorectal adenomas that were removed within a few years after patients underwent a “clean” colonoscopy during a calcium chemoprevention trial. The prevalence of mutation was associated strongly with both advanced histopathologic characteristics of the adenomas and rectal location.