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dc.contributor.authorAllione, Alessandra
dc.contributor.authorViberti, Clara
dc.contributor.authorCotellessa, Ilaria
dc.contributor.authorCatalano, Chiara
dc.contributor.authorCasalone, Elisabetta
dc.contributor.authorCugliari, Giovanni
dc.contributor.authorRusso, Alessia
dc.contributor.authorGuarrera, Simonetta
dc.contributor.authorMirabelli, Dario
dc.contributor.authorSacerdote, Carlotta
dc.contributor.authorGentile, Marco
dc.contributor.authorEichelmann, Fabian
dc.contributor.authorSchulze, Matthias B.
dc.contributor.authorHarlid, Sophia
dc.contributor.authorEriksen, Anne Kirstine
dc.contributor.authorTjønneland, Anne
dc.contributor.authorAndersson, Martin
dc.contributor.authorDollé, Martijn E.T.
dc.contributor.authorVan Puyvelde, Heleen
dc.contributor.authorWeiderpass, Elisabete
dc.contributor.authorRodriguez-Barranco, Miguel
dc.contributor.authorAgudo, Antonio
dc.contributor.authorHeath, Alicia K.
dc.contributor.authorChirlaque, María-Dolores
dc.contributor.authorTruong, Thérèse
dc.contributor.authorDragic, Dzevka
dc.contributor.authorSeveri, Gianluca
dc.contributor.authorSieri, Sabina
dc.contributor.authorSandanger, Torkjel M
dc.contributor.authorArdanaz, Eva
dc.contributor.authorVineis, Paolo
dc.contributor.authorMatullo, Giuseppe
dc.date.accessioned2023-03-16T08:14:11Z
dc.date.available2023-03-16T08:14:11Z
dc.date.issued2022-10-28
dc.description.abstractMalignant pleural mesothelioma (MPM) is a rare and aggressive cancer mainly caused by asbestos exposure. Specific and sensitive noninvasive biomarkers may facilitate and enhance screening programs for the early detection of cancer. We investigated DNA methylation (DNAm) profiles in MPM prediagnostic blood samples in a case-control study nested in the European Prospective Investigation into Cancer and nutrition (EPIC) cohort, aiming to characterise DNAm biomarkers associated with MPM. From the EPIC cohort, we included samples from 135 participants who developed MPM during 20 years of follow-up and from 135 matched, cancer-free, controls. For the discovery phase we selected EPIC participants who developed MPM within 5 years from enrolment (n = 36) with matched controls. We identified nine differentially methylated CpGs, selected by 10-fold cross-validation and correlation analyses: cg25755428 (MRI1), cg20389709 (KLF11), cg23870316, cg13862711 (LHX6), cg06417478 (HOOK2), cg00667948, cg01879420 (AMD1), cg25317025 (RPL17) and cg06205333 (RAP1A). Receiver operating characteristic (ROC) analysis showed that the model including baseline characteristics (age, sex and PC1wbc) along with the nine MPM-related CpGs has a better predictive value for MPM occurrence than the baseline model alone, maintaining some performance also at more than 5 years before diagnosis (area under the curve [AUC] < 5 years = 0.89; AUC 5-10 years = 0.80; AUC >10 years = 0.75; baseline AUC range = 0.63-0.67). DNAm changes as noninvasive biomarkers in prediagnostic blood samples of MPM cases were investigated for the first time. Their application can improve the identification of asbestos-exposed individuals at higher MPM risk to possibly adopt more intensive monitoring for early disease identification.en_US
dc.identifier.citationAllione, Viberti, Cotellessa, Catalano, Casalone, Cugliari, Russo, Guarrera, Mirabelli, Sacerdote, Gentile, Eichelmann, Schulze, Harlid, Eriksen, Tjønneland, Andersson, Dollé, Van Puyvelde, Weiderpass, Rodriguez-Barranco, Agudo, Heath, Chirlaque, Truong, Dragic, Severi, Sieri, Sandanger, Ardanaz, Vineis, Matullo. Blood cell DNA methylation biomarkers in preclinical malignant pleural mesothelioma: The EPIC prospective cohort. International Journal of Cancer. 2022en_US
dc.identifier.cristinIDFRIDAID 2087024
dc.identifier.doi10.1002/ijc.34339
dc.identifier.issn0020-7136
dc.identifier.issn1097-0215
dc.identifier.urihttps://hdl.handle.net/10037/28766
dc.language.isoengen_US
dc.publisherWileyen_US
dc.relation.journalInternational Journal of Cancer
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2022 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titleBlood cell DNA methylation biomarkers in preclinical malignant pleural mesothelioma: The EPIC prospective cohorten_US
dc.type.versionacceptedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's license is described as Attribution 4.0 International (CC BY 4.0)