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@ARTICLE{Robinson:179389,
      author       = {N. Robinson and J. Casement and M. J. Gunter and I.
                      Huybrechts and A. Agudo and M. R. Barranco and F. Eichelmann
                      and T. Johnson$^*$ and R. Kaaks$^*$ and V. Pala and S.
                      Panico and T. M. Sandanger and M. B. Schultze and R. C.
                      Travis and R. Tumino and P. Vineis and E. Weiderpass and R.
                      Skinner and L. Sharp and J. A. McKay and G. Strathdee},
      title        = {{A}nti-cancer therapy is associated with long-term
                      epigenomic changes in childhood cancer survivors.},
      journal      = {British journal of cancer},
      volume       = {127},
      number       = {2},
      issn         = {0007-0920},
      address      = {Edinburgh},
      publisher    = {Nature Publ. Group},
      reportid     = {DKFZ-2022-00640},
      pages        = {288-300},
      year         = {2022},
      note         = {2022 Jul;127(2):288-300},
      abstract     = {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.},
      cin          = {C020},
      ddc          = {610},
      cid          = {I:(DE-He78)C020-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35354948},
      doi          = {10.1038/s41416-022-01792-9},
      url          = {https://inrepo02.dkfz.de/record/179389},
}