Print Email Facebook Twitter Dietary folate and APC mutations in sporadic colorectal cancer Title Dietary folate and APC mutations in sporadic colorectal cancer Author de Vogel, S. van Engeland, M. Lüchtenborg, M. de Bruïne, A.P. Roemen, G.M.J.M. Lentjes, M.H.F.M. Goldbohm, R.A. van den Brandt, P.A. de Goeij, A.F.P.M. Weijenberg, M.P. TNO Kwaliteit van Leven Publication year 2006 Abstract Folate deficiency has been associated with colorectal cancer risk and may be involved in colorectal carcinogenesis through increased chromosome instability, gene mutations, and aberrant DNA methylation. Within the Netherlands Cohort Study on diet and cancer, we investigated the associations between dietary folate intake and colorectal cancer risk with (APC+) and without (APC-) truncating APC mutations, accounting for hMLH1 expression and K-ras mutations. In total, 528 cases and 4200 subcohort members were available for data analyses of the study cohort (n = 120,852) from a follow-up period between 2.3 and 7.3 y after baseline. Adjusted gender-specific incidence rate ratios (RR) over tertiles of folate intake were calculated in case-cohort analyses for colon and rectal cancer. Although relatively high folate intake was not associated with overall colorectal cancer risk, it reduced the risk of APC- colon tumors in men (RR 0.58, 95% CI 0.32-1.05, P trend = 0.06 for the highest vs. lowest tertile of folate intake). In contrast, it was positively associated with APC+ colon tumors in men (highest vs. lowest tertile: RR 2.77, 95% CI 1.29-5.95, Ptrend = 0.008) and was even stronger when the lack of hMLH1 expression and K-ras mutations were excluded (RR 3.99, 95% CI 1.43-11.14, Ptrend = 0.007). Such positive associations were not observed among women; nor was folate intake associated with rectal cancer when APC mutation status was taken into account. Relatively high folate consumption reduced the risk of APC- colon tumors, but folate intake was positively associated with APC+ colon tumors among men. These opposite results may indicate that folate enhances colorectal carcinogenesis through a distinct APC mutated pathway. © 2006 American Society for Nutrition. Subject NutritionFood and Chemical Risk Analysisfolic acidprotein MLH1adultagedarticlecancer riskcolon polyposiscolorectal cancercontrolled studydietary intakefemalegene mutationhumanhuman tissueincidencemajor clinical studymaleNetherlandsoncogene K rasprotein expressionrectum cancervitamin intakeAgedCarrier ProteinsCohort StudiesColonic NeoplasmsColorectal NeoplasmsDietDNA, NeoplasmFemaleFolic AcidGenes, APCHumansMaleMiddle AgedMutationNuclear ProteinsPatient SelectionProportional Hazards ModelsQuestionnairesRectal Neoplasms To reference this document use: http://resolver.tudelft.nl/uuid:0c1e359a-4236-4bec-86ee-5a5c38b9e6ea TNO identifier 239702 ISSN 0022-3166 Source Journal of Nutrition, 136 (12), 3015-3021 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.