Print Email Facebook Twitter Associations of dietary methyl donor intake with MLH1 promoter hypermethylation and related molecular phenotypes in sporadic colorectal cancer Title Associations of dietary methyl donor intake with MLH1 promoter hypermethylation and related molecular phenotypes in sporadic colorectal cancer Author de Vogel, S. Bongaerts, B.W.C. Wouters, K.A.D. Kester, A.D.M. Schouten, L.J. de Goeij, A.F.P.M. de Bruïne, A.P. Goldbohm, R.A. van den Brandt, P.A. van Engeland, M. Weijenberg, M.P. TNO Kwaliteit van Leven Publication year 2008 Abstract Intake of dietary factors that serve as methyl group donors may influence promoter hypermethylation in colorectal carcinogenesis. We investigated whether dietary folate, vitamin B2 and vitamin B6, methionine and alcohol were associated with mutL homologue 1 (MLH1) hypermethylation and the related molecular phenotypes of MLH1 protein expression, microsatellite instability (MSI) and BRAF mutations in patients with colorectal carcinomas. Within the Netherlands Cohort Study on diet and cancer (n = 120 852), 648 cases (367 men and 281 women) and 4059 subcohort members were available for data analyses from a follow-up period between 2.3 and 7.3 years after baseline. Gender-specific adjusted incidence rate ratios (RRs) were calculated over categories of dietary intake in case-cohort analyses. The intakes of folate, vitamin B2, methionine and alcohol were not associated with risk of tumors showing MLH1 hypermethylation, those lacking MLH1 protein expression or with MSI. Among men, we observed strong positive associations between folate and BRAF-mutated tumors (RR = 3.04 for the highest versus lowest tertile of intake, Ptrend = 0.03) and between vitamin B6 and tumors showing MLH1 hypermethylation (highest versus lowest tertile: RR = 3.23, Ptrend = 0.03). Among women, the relative risks of tumors with BRAF mutations or MLH1 hypermethylation were also increased in the highest tertiles of folate and vitamin B6 intake, respectively, but these did not reach statistical significance. The positive associations between folate intake and tumors harboring BRAF mutations and between vitamin B6 intake and those showing MLH1 hypermethylation were most pronounced among men and may suggest that these vitamins enhance colorectal cancer risk through genetic as well as epigenetic aberrations. © The Author 2008. Published by Oxford University Press. All rights reserved. Subject HealthAlcohol consumptionCancer incidenceCancer riskCohort analysisColon carcinogenesisColorectal carcinomaDietary intakeEpigeneticsGene mutationMicrosatellite instabilityNetherlandsPhenotypePromoter regionProtein expressionProtein methylationSex differenceVitamin intakeAdaptor Proteins, Signal TransducingAgedCohort StudiesColorectal NeoplasmsDietDNA MethylationDNA, NeoplasmFemaleFolic AcidHumansMaleMethionineMicrosatellite RepeatsMiddle AgedMutationNetherlandsNuclear ProteinsPhenotypePromoter Regions (Genetics)Proto-Oncogene Proteins B-rafQuestionnairesRiboflavinVitamin B 12Vitamin B 6 To reference this document use: http://resolver.tudelft.nl/uuid:7aeaae8a-043b-4dd8-9e51-90d4a088deb4 DOI https://doi.org/10.1093/carcin/bgn074 TNO identifier 241020 ISSN 0143-3334 Source Carcinogenesis, 29 (9), 1765-1773 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.