Cisplatin treatment of testicular cancer patients introduces long-term changes in the epigenome
dc.contributor.author | Bucher-Johannessen, Cecilie | |
dc.contributor.author | Page, Christian Magnus | |
dc.contributor.author | Haugen, Trine B. | |
dc.contributor.author | Wojewodzic, Marcin | |
dc.contributor.author | Fosså, Sophie Dorothea | |
dc.contributor.author | Grotmol, Tom | |
dc.contributor.author | Haugnes, Hege Sagstuen | |
dc.contributor.author | Rounge, Trine Ballestad | |
dc.date.accessioned | 2020-01-23T07:14:53Z | |
dc.date.accessioned | 2020-04-14T13:29:21Z | |
dc.date.available | 2020-01-23T07:14:53Z | |
dc.date.available | 2020-04-14T13:29:21Z | |
dc.date.issued | 2019-12-03 | |
dc.identifier.citation | Bucher-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;11:179:1-13 | en |
dc.identifier.issn | 1868-7075 | |
dc.identifier.issn | 1868-7075 | |
dc.identifier.issn | 1868-7083 | |
dc.identifier.uri | https://hdl.handle.net/10642/8427 | |
dc.description.abstract | Background: 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 epigenomewide 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 (n = 176) and non-treated (n = 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. Results: 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 CACNA1D (involved in insulin release) as a network hub. We found nominal MetS-associations and a functional gene network with ABCG1 and NCF2 as network hubs. Conclusion: 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 |
dc.description.sponsorship | The study was funded by the Norwegian Cancer Society (grant number 190157-2017). SDF had a grant from The Radium Hospital Foundation.no 335007. | en |
dc.language.iso | en | en |
dc.publisher | BMC | en |
dc.relation.ispartofseries | Clinical Epigenetics;11, Article number: 179 (2019) | |
dc.rights | © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. | en |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Cisplatin-based chemotherapy | en |
dc.subject | Platinum | en |
dc.subject | DNA methylation | en |
dc.subject | Testicular cancer survivors | en |
dc.subject | Epigenome-wide association studies | en |
dc.subject | Epigenetics | en |
dc.title | Cisplatin treatment of testicular cancer patients introduces long-term changes in the epigenome | en |
dc.type | Journal article | en |
dc.type | Peer reviewed | en |
dc.date.updated | 2020-01-23T07:14:53Z | |
dc.description.version | publishedVersion | en |
dc.identifier.doi | https://dx.doi.org/10.1186/s13148-019-0764-4 | |
dc.identifier.cristin | 1761524 | |
dc.source.journal | Clinical Epigenetics |
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Except where otherwise noted, this item's license is described as © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.