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[Cancer Research 59, 5181-5185, October 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 5181-5185, October 15, 1999]
© 1999 American Association for Cancer Research

Epidemiology and Prevention

Risk Factors for Ki-ras Protooncogene Mutation in Sporadic Colorectal Adenomas1

María Elena Martínez2, Terese Maltzman, James R. Marshall, Janine Einspahr, Mary E. Reid, Richard Sampliner, Dennis J. Ahnen, Stanley R. Hamilton and David S. Alberts

Arizona Cancer Center [M. E. M., J. R. M., J. E., M. E. R., R. S., D. S. A.], Arizona Prevention Center [M. E. M., J. R. M.], and Department of Medicine [R. S., D. S. A.], University of Arizona, Tucson, Arizona 85724; University of Colorado Health Sciences Center, Denver, Colorado 80220 [T. M., D. J. A.]; Department of Veterans Affairs Medical Center, Denver, Colorado 80220 [T. M., D. J. A.]; Veterans Affairs Medical Center, Tucson, Arizona 85723 [R. S.]; and M. D. Anderson Cancer Center, Houston, Texas 77030 [S. R. H.]

The Ki-ras protooncogene frequently is mutated in colorectal adenocarcinomas, but the etiology of this molecular event is uncertain. We investigated the association between variables known or suspected to be related to risk for colorectal cancer and the occurrence of Ki-ras mutations in colorectal adenomas. This study was conducted among 678 male and female participants, 40–80 years of age, enrolled in a phase III trial testing the effects of a wheat bran fiber supplement on adenoma recurrence. Exposure information on the risk factors of interest was assessed through self-administered questionnaires. Mutations in codons 12 and 13 of the Ki-ras protooncogene were analyzed in baseline adenomas 0.5 cm or larger by PCR amplification followed by direct sequencing. Eighteen percent (120 of 678) of the participants had one or more adenoma(s) with Ki-ras mutations. A higher risk of Ki-ras mutations was associated with increasing age and a lower intake of total folate. The odds ratio (OR) for Ki-ras mutations for individuals >72 years of age was 1.98 [95% confidence interval (CI) = 1.19–3.27; P for trend = 0.008] compared with those less than 65 years of age. Compared with individuals in the lower tertile of total folate, those in the upper tertile had an ~50% lower risk of having Ki-ras mutation-positive adenomas (OR = 0.52; 95% CI = 0.30–0.88; P for trend = 0.02). There was a suggestion of a stronger inverse association of total folate with G->T transversions (OR = 0.41; 95% CI = 0.20–0.87) than G->A transitions (OR = 0.61; 95% CI = 0.31–1.21), although the CIs for the associations overlap. The results of these analyses suggest that the protective effect of folate in colon cancer observed in published studies may be mediated through folate’s effect on Ki-ras mutations.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1999 by the American Association for Cancer Research.