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Anti-cancer therapy is associated with long-term epigenomic changes in childhood cancer survivors

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.

Publication metadata

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

Pages: Epub ahead of print

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


DOI: 10.1038/s41416-022-01792-9

PubMed id: 35354948


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Funder referenceFunder name
he Newcastle Hospitals NHS Charity
JGW Patterson Foundation