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dc.contributor.authorvan Veldhoven, Karin
dc.contributor.authorPolidoro, Silvia
dc.contributor.authorBaglietto, Laura
dc.contributor.authorSeveri, Gianluca
dc.contributor.authorSacerdote, Carlotta
dc.contributor.authorPanico, Salvatore
dc.contributor.authorMattiello, Amalia
dc.contributor.authorPalli, Domenico
dc.contributor.authorMasala, Giovanna
dc.contributor.authorKrogh, Vittorio
dc.contributor.authorAgnoli, Claudia
dc.contributor.authorTumino, Rosario
dc.contributor.authorFrasca, Graziella
dc.contributor.authorFlower, Kirsty
dc.contributor.authorCurry, Ed
dc.contributor.authorOrr, Nicholas
dc.contributor.authorTomczyk, Katarzyna
dc.contributor.authorJones, Michael E.
dc.contributor.authorAshworth, Alan
dc.contributor.authorSwerdlow, Anthony
dc.contributor.authorChadeau-Hyam, Marc
dc.contributor.authorLund, Eiliv
dc.contributor.authorGarcia-Closas, Montserrat
dc.contributor.authorSandanger, Torkjel M
dc.contributor.authorFlanagan, James M.
dc.contributor.authorVineis, Paolo
dc.date.accessioned2022-04-19T11:36:23Z
dc.date.available2022-04-19T11:36:23Z
dc.date.issued2015-08-04
dc.description.abstractBackground: Interest in the potential of DNA methylation in peripheral blood as a biomarker of cancer risk is increasing. We aimed to assess whether epigenome-wide DNA methylation measured in peripheral blood samples obtained before onset of the disease is associated with increased risk of breast cancer. We report on three independent prospective nested case-control studies from the European Prospective Investigation into Cancer and Nutrition (EPIC-Italy; n = 162 matched case-control pairs), the Norwegian Women and Cancer study (NOWAC; n = 168 matched pairs), and the Breakthrough Generations Study (BGS; n = 548 matched pairs). We used the Illumina 450k array to measure methylation in the EPIC and NOWAC cohorts. Whole-genome bisulphite sequencing (WGBS) was performed on the BGS cohort using pooled DNA samples, combined to reach 50× coverage across ~16 million CpG sites in the genome including 450k array CpG sites. Mean β values over all probes were calculated as a measurement for epigenome-wide methylation.<p> <p>Results: In EPIC, we found that high epigenome-wide methylation was associated with lower risk of breast cancer (odds ratio (OR) per 1 SD = 0.61, 95 % confidence interval (CI) 0.47–0.80; −0.2 % average difference in epigenome-wide methylation for cases and controls). Specifically, this was observed in gene bodies (OR = 0.51, 95 % CI 0.38–0.69) but not in gene promoters (OR = 0.92, 95 % CI 0.64–1.32). The association was not replicated in NOWAC (OR = 1.03 95 % CI 0.81–1.30). The reasons for heterogeneity across studies are unclear. However, data from the BGS cohort was consistent with epigenome-wide hypomethylation in breast cancer cases across the overlapping 450k probe sites (difference in average epigenome-wide methylation in case and control DNA pools = −0.2 %).<p> <p>Conclusions: We conclude that epigenome-wide hypomethylation of DNA from pre-diagnostic blood samples may be predictive of breast cancer risk and may thus be useful as a clinical biomarker.en_US
dc.identifier.citationvan Veldhoven, Polidoro S, Baglietto L, Severi G, Sacerdote C, Panico S, Mattiello A, Palli D, Masala G, Krogh V, Agnoli C, Tumino R, Frasca, Flower, Curry, Orr N, Tomczyk, Jones, Ashworth A, Swerdlow A, Chadeau-Hyam M, Lund e, Garcia-Closas M, Sandanger TM, Flanagan JM, Vineis P. Epigenome-wide association study reveals decreased average methylation levels years before breast cancer diagnosis. Clinical Epigenetics. 2015;7:67en_US
dc.identifier.cristinIDFRIDAID 1330833
dc.identifier.doi10.1186/s13148-015-0104-2
dc.identifier.issn1868-7075
dc.identifier.issn1868-7083
dc.identifier.urihttps://hdl.handle.net/10037/24803
dc.language.isoengen_US
dc.publisherBMCen_US
dc.relation.journalClinical Epigenetics
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7-ENVIRONMENT/308610/EU/Environmental exposures that drive disease/EXPOSOMICS/en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2015 The Author(s)en_US
dc.titleEpigenome-wide association study reveals decreased average methylation levels years before breast cancer diagnosisen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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