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dc.contributor.authorRobinson, Natassia
dc.contributor.authorCasement, John
dc.contributor.authorGunter, Marc J.
dc.contributor.authorHuybrechts, Inge
dc.contributor.authorAgudo, Antonio
dc.contributor.authorBarranco, Miguel Rodríguez
dc.contributor.authorEichelmann, Fabian
dc.contributor.authorJohnson, Theron
dc.contributor.authorKaaks, Rudolf
dc.contributor.authorPala, Valeria
dc.contributor.authorPanico, Salvatore
dc.contributor.authorSandanger, Torkjel M
dc.contributor.authorSchultze, Matthias B.
dc.contributor.authorTravis, Ruth C.
dc.contributor.authorTumino, Rosario
dc.contributor.authorVineis, Paolo
dc.contributor.authorWeiderpass, Elisabete
dc.contributor.authorSkinner, Roderick
dc.contributor.authorSharp, Linda
dc.contributor.authorMcKay, Jill A
dc.contributor.authorStrathdee, Gordon
dc.date.accessioned2022-08-29T11:46:11Z
dc.date.available2022-08-29T11:46:11Z
dc.date.issued2022-03-30
dc.description.abstractBACKGROUND: Childhood cancer survivors (CCS) exhibit significantly increased chronic diseases and premature death. Abnormalities in DNA methylation are associated with development of chronic diseases and reduced life expectancy. We investigated the hypothesis that anti-cancer treatments are associated with long-term DNA methylation changes that could be key drivers of adverse late health effects.<p> <p>METHODS: Genome-wide DNA methylation was assessed using MethylationEPIC arrays in paired samples (before/after therapy) from 32 childhood cancer patients. Separately, methylation was determined in 32 samples from different adult CCS (mean 22-years post-diagnosis) and compared with cancer-free controls (n = 284). <p>RESULTS: Widespread DNA methylation changes were identified post-treatment in childhood cancer patients, including 146 differentially methylated regions (DMRs), which were consistently altered in the 32 post-treatment samples. Analysis of adult CCS identified matching methylation changes at 107/146 of the DMRs, suggesting potential long-term retention of post-therapy changes. Adult survivors also exhibited epigenetic age acceleration, independent of DMR methylation. Furthermore, altered methylation at the DUSP6 DMR was significantly associated with early mortality, suggesting altered methylation may be prognostic for some late adverse health effects in CCS. <p>CONCLUSIONS: These novel methylation changes could serve as biomarkers for assessing normal cell toxicity in ongoing treatments and predicting long-term health outcomes in CCS.en_US
dc.identifier.citationRobinson, Casement, Gunter, Huybrechts, Agudo, Barranco, Eichelmann, Johnson, Kaaks, Pala, Panico, Sandanger, Schultze, Travis, Tumino, Vineis, Weiderpass, Skinner, Sharp, McKay, Strathdee. Anti-cancer therapy is associated with long-term epigenomic changes in childhood cancer survivors. British Journal of Cancer. 2022en_US
dc.identifier.cristinIDFRIDAID 2030671
dc.identifier.doi10.1038/s41416-022-01792-9
dc.identifier.issn0007-0920
dc.identifier.issn1532-1827
dc.identifier.urihttps://hdl.handle.net/10037/26458
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.relation.journalBritish Journal of Cancer
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2022 The Author(s)en_US
dc.titleAnti-cancer therapy is associated with long-term epigenomic changes in childhood cancer survivorsen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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