RT Journal Article T1 Anti-cancer therapy is associated with long-term epigenomic changes in childhood cancer survivors. A1 Robinson, Natassia A1 Casement, John A1 Gunter, Marc J A1 Huybrechts, Inge A1 Agudo, Antonio A1 Barranco, Miguel Rodriguez A1 Eichelmann, Fabian A1 Johnson, Theron A1 Kaaks, Rudolf A1 Pala, Valeria A1 Panico, Salvatore A1 Sandanger, Torkjel M A1 Schultze, Matthias B A1 Travis, Ruth C A1 Tumino, Rosario A1 Vineis, Paolo A1 Weiderpass, Elisabete A1 Skinner, Roderick A1 Sharp, Linda A1 McKay, Jill A A1 Strathdee, Gordon K1 Cancer therapy K1 DNA methylation K1 Paediatric cancer AB 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. 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). 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. These novel methylation changes could serve as biomarkers for assessing normal cell toxicity in ongoing treatments and predicting long-term health outcomes in CCS. PB Nature Publishing Group YR 2022 FD 2022-03-30 LK http://hdl.handle.net/10668/19523 UL http://hdl.handle.net/10668/19523 LA en NO Robinson N, Casement J, Gunter MJ, Huybrechts I, Agudo A, Barranco MR, et al. Anti-cancer therapy is associated with long-term epigenomic changes in childhood cancer survivors. Br J Cancer. 2022 Jul;127(2):288-300. doi: 10.1038/s41416-022-01792-9. DS RISalud RD Apr 20, 2025