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Carcinogenesis Advance Access originally published online on April 29, 2004
Carcinogenesis 2004 25(9):1619-1628; doi:10.1093/carcin/bgh177
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Carcinogenesis vol.25 no.9 © Oxford University Press 2004; all rights reserved.

ARTICLE

Fat and K-ras mutations in sporadic colorectal cancer in The Netherlands Cohort Study

Mirian Brink1, Matty P. Weijenberg1,5, Anton F. P. M. de Goeij2, Leo J. Schouten1, Femke D. H. Koedijk1, Guido M. J. M. Roemen3, Marjolein H. F. M. Lentjes3, Adriaan P. de Bruïne2, R.Alexandra Goldbohm4 and Piet A. van den Brandt1

1 Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Department of Epidemiology, Maastricht University, PO Box 616, 6200 MD, Maastricht, 2 Research Institute Growth and Development (GROW), Department of Pathology, Maastricht University, 3 NUTRIM, Department of Pathology, Maastricht University, and 4 TNO Nutrition and Food Research, PO Box 360, 3700 AJ Zeist, The Netherlands

5 To whom correspondence should be addressed Email: mp.weijenberg{at}epid.unimaas.nl

Associations between dietary intake of various fats and specific K-ras mutations in colorectal cancer (CRC) were investigated within the framework of The Netherlands Cohort Study on diet and cancer (NLCS). After 7.3 years of follow-up and with exclusion of the first 2.3 years, 448 colon and 160 rectal cancer patients and 2948 subcohort members (55–69 years at baseline) were available for data-analyses. Mutation analysis of the K-ras gene was performed on all archival colon and rectal adenocarcinoma specimens. Case-cohort analyses were used to compute adjusted incidence rate ratios (RR) and 95% confidence intervals (CI) for colon and rectal cancer cases and for K-ras mutation subgroups. The intake of total, saturated and monounsaturated fat was not significantly associated with colon or rectal cancer. High intake of dietary polyunsaturated fat and, specifically, linoleic acid is associated with an increased risk of mutated K-ras colon tumours. The RRs for 1 SD of increase of polyunsaturated fat and linoleic acid were 1.21 (95% CI 1.05–1.41) and 1.22 (95% CI 1.05–1.42), respectively, and similar associations were observed for both G > A transitions and G > T or G > C transversions in the colon. In contrast, no significant associations were observed with rectal cancer risk, overall nor with specific K-ras mutation status. A high intake of polyunsaturated fat, in particular linoleic acid, may be an important dietary risk factor for K-ras mutated colon tumours, possibly by generating G > A transitions or G > T or G > C transversions in the K-ras oncogene.


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