TY  - JOUR
AU  - Robinson, Natassia
AU  - Casement, John
AU  - Gunter, Marc J
AU  - Huybrechts, Inge
AU  - Agudo, Antonio
AU  - Barranco, Miguel Rodríguez
AU  - Eichelmann, Fabian
AU  - Johnson, Theron
AU  - Kaaks, Rudolf
AU  - Pala, Valeria
AU  - Panico, Salvatore
AU  - Sandanger, Torkjel M
AU  - Schultze, Matthias B
AU  - Travis, Ruth C
AU  - Tumino, Rosario
AU  - Vineis, Paolo
AU  - Weiderpass, Elisabete
AU  - Skinner, Roderick
AU  - Sharp, Linda
AU  - McKay, Jill A
AU  - Strathdee, Gordon
TI  - Anti-cancer therapy is associated with long-term epigenomic changes in childhood cancer survivors.
JO  - British journal of cancer
VL  - 127
IS  - 2
SN  - 0007-0920
CY  - Edinburgh
PB  - Nature Publ. Group
M1  - DKFZ-2022-00640
SP  - 288-300
PY  - 2022
N1  - 2022 Jul;127(2):288-300
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.
LB  - PUB:(DE-HGF)16
C6  - pmid:35354948
DO  - DOI:10.1038/s41416-022-01792-9
UR  - https://inrepo02.dkfz.de/record/179389
ER  -