dc.contributor.author | Robinson, Natassia | |
dc.contributor.author | Casement, John | |
dc.contributor.author | Gunter, Marc J. | |
dc.contributor.author | Huybrechts, Inge | |
dc.contributor.author | Agudo, Antonio | |
dc.contributor.author | Barranco, Miguel Rodríguez | |
dc.contributor.author | Eichelmann, Fabian | |
dc.contributor.author | Johnson, Theron | |
dc.contributor.author | Kaaks, Rudolf | |
dc.contributor.author | Pala, Valeria | |
dc.contributor.author | Panico, Salvatore | |
dc.contributor.author | Sandanger, Torkjel M | |
dc.contributor.author | Schultze, Matthias B. | |
dc.contributor.author | Travis, Ruth C. | |
dc.contributor.author | Tumino, Rosario | |
dc.contributor.author | Vineis, Paolo | |
dc.contributor.author | Weiderpass, Elisabete | |
dc.contributor.author | Skinner, Roderick | |
dc.contributor.author | Sharp, Linda | |
dc.contributor.author | McKay, Jill A | |
dc.contributor.author | Strathdee, Gordon | |
dc.date.accessioned | 2022-08-29T11:46:11Z | |
dc.date.available | 2022-08-29T11:46:11Z | |
dc.date.issued | 2022-03-30 | |
dc.description.abstract | BACKGROUND: 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.citation | Robinson, 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. 2022 | en_US |
dc.identifier.cristinID | FRIDAID 2030671 | |
dc.identifier.doi | 10.1038/s41416-022-01792-9 | |
dc.identifier.issn | 0007-0920 | |
dc.identifier.issn | 1532-1827 | |
dc.identifier.uri | https://hdl.handle.net/10037/26458 | |
dc.language.iso | eng | en_US |
dc.publisher | Springer Nature | en_US |
dc.relation.journal | British Journal of Cancer | |
dc.rights.accessRights | openAccess | en_US |
dc.rights.holder | Copyright 2022 The Author(s) | en_US |
dc.title | Anti-cancer therapy is associated with long-term epigenomic changes in childhood cancer survivors | en_US |
dc.type.version | publishedVersion | en_US |
dc.type | Journal article | en_US |
dc.type | Tidsskriftartikkel | en_US |
dc.type | Peer reviewed | en_US |