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dc.contributor.authorPerrier, Flavie
dc.contributor.authorViallon, Vivian
dc.contributor.authorAmbatipudi, Srikant
dc.contributor.authorGhantous, Akram
dc.contributor.authorCuenin, Cyrille
dc.contributor.authorHernandez-Vargas, Hector
dc.contributor.authorChajès, Véronique
dc.contributor.authorBaglietto, Laura
dc.contributor.authorMatejcic, Marco
dc.contributor.authorMoreno-Macías, Hortensia
dc.contributor.authorKühn, Tilman
dc.contributor.authorBoeing, Heiner
dc.contributor.authorKarakatsani, Anna
dc.contributor.authorKotanidou, Anastasia
dc.contributor.authorTrichopoulou, Antonia
dc.contributor.authorSieri, Sabina
dc.contributor.authorPanico, Salvatore
dc.contributor.authorFasanelli, Francesca
dc.contributor.authorDollé, Martijn
dc.contributor.authorOnland-Moret, Charlotte
dc.contributor.authorSluijs, Ivonne
dc.contributor.authorWeiderpass, Elisabete
dc.contributor.authorQuirós, José Ramón
dc.contributor.authorAgudo, Antonio
dc.contributor.authorHuerta, José María
dc.contributor.authorArdanaz, Eva
dc.contributor.authorDorronsoro, Miren
dc.contributor.authorTong, Tammy Y.N.
dc.contributor.authorTsilidis, Konstantinos K.
dc.contributor.authorRiboli, Elio
dc.contributor.authorGunter, Mark J.
dc.contributor.authorHerceg, Zdenko
dc.contributor.authorFerrari, Pietro
dc.contributor.authorRomieu, Isabelle
dc.date.accessioned2020-01-08T12:52:43Z
dc.date.available2020-01-08T12:52:43Z
dc.date.issued2019-04-02
dc.description.abstract<i>Background</i> - There 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.<p> <p><i>Results</i> - 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<sub>val</sub> = 0.029 and q<sub>val</sub> = 0.048, respectively. Interestingly, the DMR analysis revealed a total of 24 and 90 regions associated with dietary folate and alcohol, respectively. For alcohol intake, 6 of the 15 most significant DMRs were identified through FL.<p> <p><i>Conclusions</i> - 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 <i>GSDMD</i> and <i>HOXA5</i> 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. Fjernen_US
dc.identifier.citationPerrier F, Viallon V, Ambatipudi S, Ghantous A, Cuenin C, Hernandez-Vargas H, Chajès V, Baglietto L, Matejcic M, Moreno-Macías H, Kühn T, Boeing H, Karakatsani A, Kotanidou A, Trichopoulou A, Sieri S, Panico S, Fasanelli F, Dollé M, Onland-Moret C, Sluijs I, Weiderpass E, Quirós JR, Agudo A, Huerta JM, Ardanaz E, Dorronsoro M, Tong TY, Tsilidis KK, Riboli E, Gunter MJ, Herceg Z, Ferrari P, Romieu I. Association of leukocyte DNA methylation changes with dietary folate and alcohol intake in the EPIC study. Clinical Epigenetics. 2019;11:57:1-13en_US
dc.identifier.cristinIDFRIDAID 1712718
dc.identifier.doi10.1186/s13148-019-0637-x
dc.identifier.issn1868-7075
dc.identifier.issn1868-7083
dc.identifier.urihttps://hdl.handle.net/10037/17035
dc.language.isoengen_US
dc.publisherBMCen_US
dc.relation.journalClinical Epigenetics
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/?/EU/?/?/en_US
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/DG-SANCO/?/EU/?/?/en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2019 The Author(s)en_US
dc.subjectVDP::Medical disciplines: 700en_US
dc.subjectVDP::Medisinske Fag: 700en_US
dc.titleAssociation of leukocyte DNA methylation changes with dietary folate and alcohol intake in the EPIC studyen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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