K-ras mutations in incident sporadic colorectal adenomas

Authors

  • Elizabeth L. R. Barry Ph.D.,

    Corresponding author
    1. Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, New Hampshire
    • Department of Community and Family Medicine, Dartmouth Medical School, Section of Biostatistics and Epidemiology, Evergreen Center, 46 Centerra Parkway, Suite 300, Lebanon, NH 03766
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    • Fax: (603) 650-3473

  • John A. Baron M.D.,

    1. Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, New Hampshire
    2. Department of Medicine, Dartmouth Medical School, Lebanon, New Hampshire
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  • Maria V. Grau M.D., M.P.H.,

    1. Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, New Hampshire
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  • Kristin Wallace Ph.D.,

    1. Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, New Hampshire
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  • Robert W. Haile Dr.PH.

    1. Department of Preventive Medicine, University of Southern California, Los Angeles, California
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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. ≤ 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.

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