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

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Author: Brink, M. · Weijenberg, M.P. · Goeij, A.F.P.M. de · Schouten, L.J. · Koedijk, F.D.H. · Roemen, G.M.J.M. · Lentjes, M.H.F.M. · Bruïne, A.P. de · Goldbohm, R.A. · Brandt, P.A. van den
Institution: TNO Voeding
Source:Carcinogenesis, 9, 25, 1619-1628
Identifier: 237976
doi: doi:10.1093/carcin/bgh177
Keywords: Health · Food and Chemical Risk Analysis · adenine · fat · guanine · K ras protein · linoleic acid · monounsaturated fatty acid · polyunsaturated fatty acid · thymine · unsaturated fatty acid · adult · aged · article · cancer incidence · cancer patient · cancer risk · cohort analysis · colon cancer · colon carcinogenesis · colorectal cancer · confidence interval · controlled study · data analysis · fat intake · female · follow up · gene mutation · human · major clinical study · male · mutational analysis · Netherlands · nucleic acid base substitution · oncogene K ras · priority journal · rectum cancer · risk factor · Aged · Cohort Studies · Colonic Neoplasms · Diet · Fats · Female · Follow-Up Studies · Genes, ras · Humans · Male · Middle Aged · Mutation · Netherlands · Rectal Neoplasms


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. © Oxford University Press 2004; all rights reserved.