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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\u2010control 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\u2009years of follow\u2010up and from 135 matched, cancer\u2010free, controls. For the discovery phase we selected EPIC participants who developed MPM within 5\u2009years from enrolment (n\u00a0=\u00a036) with matched controls. We identified nine differentially methylated CpGs, selected by 10\u2010fold cross\u2010validation and correlation analyses: cg25755428 (<jats:italic>MRI1<\/jats:italic>), cg20389709 (<jats:italic>KLF11<\/jats:italic>), cg23870316, cg13862711 (<jats:italic>LHX6<\/jats:italic>), cg06417478 (<jats:italic>HOOK2<\/jats:italic>), cg00667948, cg01879420 (<jats:italic>AMD1<\/jats:italic>), cg25317025 (<jats:italic>RPL17<\/jats:italic>) and cg06205333 (<jats:italic>RAP1A<\/jats:italic>). Receiver operating characteristic (ROC) analysis showed that the model including baseline characteristics (age, sex and PC1wbc) along with the nine MPM\u2010related CpGs has a better predictive value for MPM occurrence than the baseline model alone, maintaining some performance also at more than 5\u2009years before diagnosis (area under the curve [AUC]\u2009&lt;\u20095\u2009years\u00a0=\u00a00.89; AUC 5\u201010\u2009years\u00a0=\u00a00.80; AUC &gt;10\u2009years\u00a0=\u00a00.75; baseline AUC range\u00a0=\u00a00.63\u20100.67). 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\u2010exposed individuals at higher MPM risk to possibly adopt more intensive monitoring for early disease identification.<\/jats:p>","DOI":"10.1002\/ijc.34339","type":"journal-article","created":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T12:45:19Z","timestamp":1666961119000},"page":"725-737","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Blood cell <scp>DNA<\/scp> methylation biomarkers in preclinical malignant pleural mesothelioma: The <scp>EPIC<\/scp> prospective cohort"],"prefix":"10.1002","volume":"152","author":[{"given":"Alessandra","family":"Allione","sequence":"first","affiliation":[{"name":"Department of Medical Sciences University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Viberti","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Cotellessa","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Catalano","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Casalone","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Cugliari","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences University of Turin  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4400-1817","authenticated-orcid":false,"given":"Simonetta","family":"Guarrera","sequence":"additional","affiliation":[{"name":"IIGM\u2014Italian Institute for Genomic Medicine, c\/o IRCCS  Turin Italy"},{"name":"Candiolo Cancer Institute FPO\u2014IRCCS  Candiolo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Mirabelli","sequence":"additional","affiliation":[{"name":"Cancer Epidemiology Unit, Department of Medical Sciences University of Turin  Turin Italy"},{"name":"Interdepartmental Center for Studies on Asbestos and Other Toxic Particulates \u201cG. 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