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Cancer. 2006 Mar 1;106(5):1036-40.

K-ras mutations in incident sporadic colorectal adenomas.

Author information

1
Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, New Hampshire 03766, USA. elizabeth.l.barry@dartmouth.edu

Abstract

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. < or = 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.

PMID:
16456810
DOI:
10.1002/cncr.21721
[Indexed for MEDLINE]
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