Persistent variations of blood DNA methylation associated with treatment exposures and risk for cardiometabolic outcomes in long-term survivors of childhood cancer in the St. Jude Lifetime Cohort

  • Nan Song (Creator)
  • Chia Wei Hsu (Contributor)
  • Haitao Pan (Contributor)
  • Yinan Zheng (Contributor)
  • Lifang Hou (Contributor)
  • Jin ah Sim (Contributor)
  • Zhenghong Li (Contributor)
  • Heather L. Mulder (Creator)
  • John Easton (Creator)
  • Emily M. Walker (Creator)
  • Geoffrey A. Neale (Creator)
  • Carmen L. Wilson (Creator)
  • Kirsten K. Ness (Creator)
  • Kevin R. Krull (Creator)
  • Deo Kumar Srivastava (Creator)
  • Yutaka Yasui (Creator)
  • Jinghui Zhang (Contributor)
  • M. M. Hudson (Creator)
  • Leslie L. Robison (Creator)
  • I. Chan Huang (Contributor)
  • Zhaoming Wang (Creator)
  • Hsu Chia-Wei (Contributor)
  • Pan Haitao (Contributor)
  • Sim Jin-Ah (Contributor)
  • Li Zhenghong (Contributor)
  • Emily Walker (Creator)
  • Yutaka Yasui (Creator)
  • Leslie L. Robison (Creator)



Abstract Background It is well-established that cancer treatment substantially increases the risk of long-term adverse health outcomes among childhood cancer survivors. However, there is limited research on the underlying mechanisms. To elucidate the pathophysiology and a possible causal pathway from treatment exposures to cardiometabolic conditions, we conducted epigenome-wide association studies (EWAS) to identify the DNA methylation (DNAm) sites associated with cancer treatment exposures and examined whether treatment-associated DNAm sites mediate associations between specific treatments and cardiometabolic conditions. Methods We included 2052 survivors (median age 33.7 years) of European ancestry from the St. Jude Lifetime Cohort Study, a retrospective hospital-based study with prospective clinical follow-up. Cumulative doses of chemotherapy and region-specific radiation were abstracted from medical records. Seven cardiometabolic conditions were clinically assessed. DNAm profile was measured using MethylationEPIC BeadChip with blood-derived DNA. Results By performing multiple treatment-specific EWAS, we identified 935 5′-cytosine-phosphate-guanine-3′ (CpG) sites mapped to 538 genes/regions associated with one or more cancer treatments at the epigenome-wide significance level (p
Date made available2021

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