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Lookup NU author(s): Natassia Robinson, John CasementORCiD, Professor Roderick Skinner, Professor Linda Sharp, Dr Jill McKay, Dr Gordon Strathdee
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2022, The Author(s). 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. 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). 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. 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.
Author(s): Robinson N, Casement J, Gunter MJ, Huybrechts I, Agudo A, Barranco MR, Eichelmann F, Johnson T, Kaaks R, Pala V, Panico S, Sandanger TM, Schultze MB, Travis RC, Tumino R, Vineis P, Weiderpass E, Skinner R, Sharp L, McKay JA, Strathdee G
Publication type: Article
Publication status: Published
Journal: British Journal of Cancer
Year: 2022
Volume: 127
Pages: 288-300
Print publication date: 20/07/2022
Online publication date: 30/03/2022
Acceptance date: 11/03/2022
Date deposited: 26/04/2022
ISSN (print): 0007-0920
ISSN (electronic): 1532-1827
Publisher: Nature Publishing Group
URL: https://doi.org/10.1038/s41416-022-01792-9
DOI: 10.1038/s41416-022-01792-9
PubMed id: 35354948
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