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dc.contributor.authorBucher-Johannessen, Cecilie
dc.contributor.authorPage, Christian Magnus
dc.contributor.authorHaugen, Trine B.
dc.contributor.authorWojewodzic, Marcin
dc.contributor.authorFosså, Sophie Dorothea
dc.contributor.authorGrotmol, Tom
dc.contributor.authorHaugnes, Hege Sagstuen
dc.contributor.authorRounge, Trine Ballestad
dc.date.accessioned2020-01-24T06:53:08Z
dc.date.available2020-01-24T06:53:08Z
dc.date.issued2019-12-03
dc.description.abstract<i>Background</i> - Cisplatin-based chemotherapy (CBCT) is part of standard treatment of several cancers. In testicular cancer (TC) survivors, an increased risk of developing metabolic syndrome (MetS) is observed. In this epigenome-wide association study, we investigated if CBCT relates to epigenetic changes (DNA methylation) and if epigenetic changes render individuals susceptible for developing MetS later in life. We analyzed methylation profiles, using the MethylationEPIC BeadChip, in samples collected ~ 16 years after treatment from 279 Norwegian TC survivors with known MetS status. Among the CBCT treated (<i>n</i> = 176) and non-treated (<i>n</i> = 103), 61 and 34 developed MetS, respectively. We used two linear regression models to identify if (i) CBCT results in epigenetic changes and (ii) epigenetic changes play a role in development of MetS. Then we investigated if these changes in (i) and (ii) links to genes, functional networks, and pathways related to MetS symptoms.<p> <p><i>Results</i> - We identified 35 sites that were differentially methylated when comparing CBCT treated and untreated TC survivors. The PTK6–RAS–MAPk pathway was significantly enriched with these sites and infers a gene network of 13 genes with <i>CACNA1D</i> (involved in insulin release) as a network hub. We found nominal MetS-associations and a functional gene network with <i>ABCG1</i> and <i>NCF2</i> as network hubs.<p> <p><i>Conclusion</i> - Our results suggest that CBCT has long-term effects on the epigenome. We could not directly link the CBCT effects to the risk of developing MetS. Nevertheless, since we identified differential methylation occurring in genes associated with conditions pertaining to MetS, we hypothesize that epigenomic changes may also play a role in the development of MetS in TC survivors. Further studies are needed to validate this hypothesis.en_US
dc.identifier.citationBucher-Johannessen C, Page CM, Haugen TB, Wojewodzic M, Fosså SD, Grotmol T, Haugnes h, Rounge TB. Cisplatin treatment of testicular cancer patients introduces long-term changes in the epigenome. Clinical Epigenetics. 2019;11:179:1-13en_US
dc.identifier.cristinIDFRIDAID 1761524
dc.identifier.doi10.1186/s13148-019-0764-4
dc.identifier.issn1868-7075
dc.identifier.issn1868-7083
dc.identifier.urihttps://hdl.handle.net/10037/17206
dc.language.isoengen_US
dc.publisherBMCen_US
dc.relation.journalClinical Epigenetics
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.titleCisplatin treatment of testicular cancer patients introduces long-term changes in the epigenomeen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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