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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
dc.contributor.author Wouters, Kim A. D.
dc.contributor.author Gottschalk, Ralph W. H.
dc.contributor.author Schooten, Frederik J.
dc.contributor.author Goeij, Anton F. P. M.
dc.contributor.author Bruïne, Adriaan P.
dc.contributor.author Goldbohm, R. Alexandra
dc.contributor.author den Brandt, Piet A.
dc.contributor.author Engeland, Manon
dc.contributor.author Weijenberg, Matty P.
dc.date.accessioned 2011-03-11T10:54:04Z
dc.date.available 2011-03-11T10:54:04Z
dc.date.issued 2010-12-14
dc.identifier.citation Cancer Causes & Control (2011) 22: 1-12 en_US
dc.identifier.issn 0957-5243
dc.identifier.uri http://dx.doi.org/10.1007/s10552-010-9659-6
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 en_US
dc.publisher Springer en
dc.rights Copyright The Author(s) 2010. This article is published with open access at Springerlink.com en_US
dc.rights.uri http://creativecommons.org/licenses/by-nc/2.5/ en_US
dc.subject Methyl donors en
dc.subject Diet–gene interactions en
dc.subject Promoter hypermethylation en
dc.subject CRC en
dc.title Dietary methyl donors, methyl metabolizing enzymes, and epigenetic regulators: diet–gene interactions and promoter CpG island hypermethylation in colorectal cancer en_US
dc.type Peer reviewed en_US
dc.type Journal article en_US
dc.subject.nsi VDP::Medical disciplines: 700 en_US
dc.rightsHolder The Author(s) 2010 en_US
dc.type.version publishedVersion en_US
bora.cristinID 830102


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Copyright The Author(s) 2010. This article is published with open access at Springerlink.com Except where otherwise noted, this item's license is described as Copyright The Author(s) 2010. This article is published with open access at Springerlink.com

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