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Dietary methyl donors, methyl metabolizing enzymes, and epigenetic regulators: diet–gene interactions and promoter CpG island hypermethylation in colorectal cancer

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dc.contributor.author De Vogel, Stefan eng
dc.contributor.author Wouters, Kim A. D. eng
dc.contributor.author Gottschalk, Ralph W. H. eng
dc.contributor.author Schooten, Frederik J. eng
dc.contributor.author Goeij, Anton F. P. M. eng
dc.contributor.author Bruïne, Adriaan P. eng
dc.contributor.author Goldbohm, R. Alexandra eng
dc.contributor.author den Brandt, Piet A. eng
dc.contributor.author Engeland, Manon eng
dc.contributor.author Weijenberg, Matty P. eng
dc.date.accessioned 2011-03-11T10:54:04Z
dc.date.available 2011-03-11T10:54:04Z
dc.date.issued 2010-12-14 eng
dc.identifier.citation Cancer Causes & Control (2011) 22: 1-12 en_US
dc.identifier.issn 0957-5243 eng
dc.identifier.uri http://hdl.handle.net/1956/4572
dc.description.abstract Dietary methyl donors might influence DNA methylation during carcinogenesis of colorectal cancer (CRC). Among 609 CRC cases and 1,663 subcohort members of the Netherlands Cohort Study on diet and cancer (n = 120,852), we estimated CRC risk according to methyl donor intake across genotypes of folate metabolizing enzymes and methyltransferases. Although diet–gene interactions were not statistically significant, methionine intake was inversely associated with CRC among subjects having both common rs2424913 and rs406193 DNMT3B C[T genotypes (highest versus lowest tertile: RR = 0.44; ptrend = 0.05). Likewise, vitamin B2 was modestly inversely associated among individuals with the MTHFR c.665CC (rs1801133) genotype (RR = 0.66; ptrend = 0.08), but with a significant reduced risk when B 1 rare allele occurred in the combination of folate metabolizing enzymes MTHFR, MTRR and MTR (RR = 0.30; ptrend = 0.005). Folate or vitamin B6 were neither inversely associated with CRC nor was methyl donor intake associated with the CpG island methylator phenotype (CIMP). Despite the absence of heterogeneity across genotypes, might an effect of methyl donors on CRC be more pronounced among individuals carrying common variants of folate metabolizing enzymes or DNA methyltransferases. Combining genotypes may assist to reveal diet associations with CRC, possibly because rare variants of related genes may collectively affect specific metabolic pathways or enzymatic functions. en_US
dc.language.iso eng eng
dc.publisher Springer eng
dc.rights Attribution-NonCommercial CC BY-NC eng
dc.rights.uri http://creativecommons.org/licenses/by-nc/2.5/ eng
dc.subject Methyl donors eng
dc.subject Diet–gene interactions eng
dc.subject Promoter hypermethylation eng
dc.subject CRC eng
dc.title Dietary methyl donors, methyl metabolizing enzymes, and epigenetic regulators: diet–gene interactions and promoter CpG island hypermethylation in colorectal cancer eng
dc.type Peer reviewed eng
dc.type Journal article eng
dc.subject.nsi VDP::Medical disciplines: 700 eng
dc.rights.holder Copyright The Author(s) 2010. This article is published with open access at Springerlink.com
dc.rights.holder The Author(s) 2010 eng
dc.type.version publishedVersion eng
bora.peerreviewed Peer reviewed eng
bora.cristinID 830102 eng
bibo.doi http://dx.doi.org/10.1007/s10552-010-9659-6 eng
dc.identifier.cristinID 830102 eng
dc.identifier.doi http://dx.doi.org/10.1007/s10552-010-9659-6


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