Associations between dietary intake and Ki-ras mutations in colon tumors: A population-based study

Martha L. Slattery, Karen Curtin, Kristin E Anderson, Khe Ni Ma, Sandra Edwards, Mark Leppert, John Potter, Donna Schaffer, Wade S. Samowitz

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Abstract

Ki-ras mutations are thought to be early events in the carcinogenic process leading to colon tumors. Dietary factors associated with colon cancer may be associated with these mutations. Data from a population-based, multicenter, case-control study of colon cancer were used to determine whether dietary factors are associated with Ki-ras mutations. Ki-ras mutations were detected by direct sequencing of codons 12 and 13 of the Ki-ras gene on exon 1 from DNA obtained from archival tissue. Ki-ras data were available for 1428 cases with valid interview data; data from 2410 controls were available for comparison with cases positive and negative for Ki-ras mutations. Mutations in the Ki-ras gene were detected in 32% of tumors. Of these mutations, 32.8% were G→A transitions in the second base of codon 12 (2G→A). Other than cruciferous vegetables, there were no nutrients or foods associated specifically with Ki-ras mutations [odds ratio (OR) for high intake relative to low intake, 0.7; 95% confidence interval (CI), 0.5-1.0]. However, evaluation of specific types of Ki-ras mutations revealed that for each of the most common types of mutation, dietary associations existed. Dietary factors involved in DNA methylation pathways were associated with 2G→A mutations. Comparison of individuals with and without Ki-ras mutations revealed that individuals with low levels of dietary folate (OR, 0.7; 95% CI, 0.4-1.3), vitamin B6 (OR, 0.5; 95% CI, 0.3-1.0), vitamin B12 (OR, 0.6; 95% CI, 0.3-1.1), and high levels of alcohol (OR, 0.7; 95% CI, 0.4-1.1) were less likely to have a 2G→A mutation. Individuals with high levels of dietary carbohydrate (OR, 2.0; 95% CI, 0.9-4.4) and a high glycemic index (OR, 1.9; 95% CI, 0.8-4.6) were more likely to have a G→A transition mutation in the second base of codon 13 (5G→A). Individuals with high levels of dietary fat (OR, 1.6; 95% CI, 0.8-3.2), saturated fat (OR, 1.7; 95% CI, 0.8-3.5), and monounsaturated fat (OR, 1.9; 95% CI, 1.0-3.7) were more likely to harbor a 2G→T mutation. Low levels of cruciferous vegetable intake and high levels of processed meat intake also were associated with fewer 5G→A, as reflected by the ORs (OR, 0.4; 95% CI, 0.2-1.0 and OR, 0.4; 95% CI 0.2-0.8, respectively). These data suggest that diet may be involved in disease pathways represented by specific Ki-ras mutations. However, given the limited information currently available on associations between specific genetic mutations in colon tumors and diet, these findings also should be viewed as hypothesis generating.

Original languageEnglish (US)
Pages (from-to)6935-6941
Number of pages7
JournalCancer Research
Volume60
Issue number24
StatePublished - Dec 15 2000

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    Slattery, M. L., Curtin, K., Anderson, K. E., Ma, K. N., Edwards, S., Leppert, M., Potter, J., Schaffer, D., & Samowitz, W. S. (2000). Associations between dietary intake and Ki-ras mutations in colon tumors: A population-based study. Cancer Research, 60(24), 6935-6941.