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
Health
Alcohol consumption
Cancer incidence
Cancer risk
Cohort analysis
Colon carcinogenesis
Colorectal carcinoma
Dietary intake
Epigenetics
Gene mutation
Microsatellite instability
Netherlands
Phenotype
Promoter region
Protein expression
Protein methylation
Sex difference
Vitamin intake
Adaptor Proteins, Signal Transducing
Aged
Cohort Studies
Colorectal Neoplasms
Diet
DNA Methylation
DNA, Neoplasm
Female
Folic Acid
Humans
Male
Methionine
Microsatellite Repeats
Middle Aged
Mutation
Netherlands
Nuclear Proteins
Phenotype
Promoter Regions (Genetics)
Proto-Oncogene Proteins B-raf
Questionnaires
Riboflavin
Vitamin B 12
Vitamin 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