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dc.contributor.authorPerrier, F
dc.contributor.authorViallon, V
dc.contributor.authorAmbatipudi, S
dc.contributor.authorGhantous, A
dc.contributor.authorCuenin, C
dc.contributor.authorHernandez-Vargas, H
dc.contributor.authorChajès, V
dc.contributor.authorBaglietto, L
dc.contributor.authorMatejcic, M
dc.contributor.authorMoreno-Macias, H
dc.contributor.authorKühn, T
dc.contributor.authorBoeing, H
dc.contributor.authorKarakatsani, A
dc.contributor.authorKotanidou, A
dc.contributor.authorTrichopoulou, A
dc.contributor.authorSieri, S
dc.contributor.authorPanico, S
dc.contributor.authorFasanelli, F
dc.contributor.authorDolle, M
dc.contributor.authorOnland-Moret, C
dc.contributor.authorSluijs, I
dc.contributor.authorWeiderpass, E
dc.contributor.authorQuirós, J R
dc.contributor.authorAgudo, A
dc.contributor.authorHuerta, J M
dc.contributor.authorArdanaz, E
dc.contributor.authorDorronsoro, M
dc.contributor.authorTong, T Y N
dc.contributor.authorTsilidis, K
dc.contributor.authorRiboli, E
dc.contributor.authorGunter, M J
dc.contributor.authorHerceg, Z
dc.contributor.authorFerrari, P
dc.contributor.authorRomieu, I
dc.date.accessioned2019-04-26T07:55:12Z
dc.date.available2019-04-26T07:55:12Z
dc.date.issued2019-04-02
dc.identifier.issn1868-7083
dc.identifier.pmid30940212
dc.identifier.doi10.1186/s13148-019-0637-x
dc.identifier.urihttp://hdl.handle.net/10029/623031
dc.description.abstractThere is increasing evidence that folate, an important component of one-carbon metabolism, modulates the epigenome. Alcohol, which can disrupt folate absorption, is also known to affect the epigenome. We investigated the association of dietary folate and alcohol intake on leukocyte DNA methylation levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Leukocyte genome-wide DNA methylation profiles on approximately 450,000 CpG sites were acquired with Illumina HumanMethylation 450K BeadChip measured among 450 women control participants of a case-control study on breast cancer nested within the EPIC cohort. After data preprocessing using surrogate variable analysis to reduce systematic variation, associations of DNA methylation with dietary folate and alcohol intake, assessed with dietary questionnaires, were investigated using CpG site-specific linear models. Specific regions of the methylome were explored using differentially methylated region (DMR) analysis and fused lasso (FL) regressions. The DMR analysis combined results from the feature-specific analysis for a specific chromosome and using distances between features as weights whereas FL regression combined two penalties to encourage sparsity of single features and the difference between two consecutive features. After correction for multiple testing, intake of dietary folate was not associated with methylation level at any DNA methylation site, while weak associations were observed between alcohol intake and methylation level at CpG sites cg03199996 and cg07382687, with q Alcohol intake was associated with methylation levels at two CpG sites. Evidence from DMR and FL analyses indicated that dietary folate and alcohol intake may be associated with genomic regions with tumor suppressor activity such as the GSDMD and HOXA5 genes. These results were in line with the hypothesis that epigenetic mechanisms play a role in the association between folate and alcohol, although further studies are warranted to clarify the importance of these mechanisms in cancer.en_US
dc.language.isoenen_US
dc.subjectAlcohol intakeen_US
dc.subjectDMRen_US
dc.subjectDNA methylationen_US
dc.subjectDietary folateen_US
dc.subjectEPIC cohorten_US
dc.subjectFused lassoen_US
dc.titleAssociation of leukocyte DNA methylation changes with dietary folate and alcohol intake in the EPIC study.en_US
dc.typeArticleen_US
dc.identifier.journalClin Epigenetics 2019; 11(1):57en_US
dc.source.journaltitleClinical epigenetics


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