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Carcinogenesis Advance Access published online on April 29, 2004
Carcinogenesis, doi:10.1093/carcin/bgh177
© 2004 by Oxford University Press
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Received December 8, 2003
Revised April 2, 2004
Accepted April 23, 2004

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

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

Mirian Brink 1, Matty P. Weijenberg 1*, Anton F. P. M. de Goeij 2, Leo J. Schouten 1, Femke D. H. Koedijk 1, Guido M. J. M. Roemen 3, Marjolein H. F. M. Lentjes 3, Adriaan P. de Bruïne 2, R. Alexandra Goldbohm 4, Piet A. van den Brandt 1

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

* To whom correspondence should be addressed. E-mail: MP.Weijenberg{at}epid.unimaas.nl.


  Abstract

Background/Aim: 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).

Methods: After 7.3 years of follow-up and with exclusion of the first 2.3 years, 448 colon and 160 rectal cancer patients and 3048 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.

Results: Intake of total, saturated and mono-unsaturated fat was not significantly associated with colon or rectal cancer. High intake of dietary poly-unsaturated fat and, specifically, linoleic acid is associated with an increased risk of mutated K-ras colon tumours. The RRs for one standard deviation of increase of poly-unsaturated 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.

Conclusions: A high intake of poly-unsaturated 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.

Key Words: {omega}-6 poly-unsaturated fat, colon, rectum, K-ras, cohort


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