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<p>Childhood cancer survivors face increased cardiometabolic risks from cancer treatment exposures, yet mechanisms remain unclear. Here, epigenome-wide analysis identifies 1893 DNA methylation (DNAm) sites in peripheral-blood-mononuclear-cells (PBMCs) associated with at least one cardiometabolic risk factor (CMRF), including obesity (<i>n</i> = 1720), abnormal glucose (<i>n</i> = 201), hypertriglyceridemia (<i>n</i> = 145), hypercholesterolemia (<i>n</i> = 38) and hypertension (<i>n</i> = 34) in 2938 survivors from the St. Jude Lifetime Cohort. A core set of five DNAm sites near <i>CPT1A</i> and <i>LMNA</i> is associated with all CMRFs. Mediation analyses identify 24 sites mediating associations between treatments and CMRFs, implicating inflammatory and metabolic pathways. Notably, cg20370568, a cis-expression quantitative trait methylation site for <i>ANTXR2</i>, mediates 20% of the effect of body-trunk-radiotherapy on abnormal glucose. These findings suggest that prior genotoxic cancer treatments may become biologically embedded through DNAm variations that could contribute to cardiometabolic dysfunction and highlight candidate biomarkers for refining risk stratification and guiding intervention strategies in survivorship care.</p>

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Epigenome-wide analysis identifies DNA methylation mediators of treatment-related cardiometabolic risk in survivors of childhood cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月23日

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  • Tiffany Eulalio,
  • Yoonji Kim,
  • Xiaoxi Meng,
  • Noel-Marie Plonski,
  • Kyla Shelton,
  • Heather Mulder,
  • Emily Plyler,
  • John Easton,
  • Xiang Chen,
  • Jinghui Zhang,
  • Emily Walker,
  • Geoffrey Neale,
  • Min Ni,
  • John T. Lucas Jr.,
  • Nilanjan Chatterjee,
  • Ziqiao Wang,
  • Deokumar Srivastava,
  • Bonnie Ky,
  • Stephanie B. Dixon,
  • Kirsten K. Ness,
  • Melissa M. Hudson,
  • Gregory T. Armstrong,
  • Zhaoming Wang

摘要

Childhood cancer survivors face increased cardiometabolic risks from cancer treatment exposures, yet mechanisms remain unclear. Here, epigenome-wide analysis identifies 1893 DNA methylation (DNAm) sites in peripheral-blood-mononuclear-cells (PBMCs) associated with at least one cardiometabolic risk factor (CMRF), including obesity (n = 1720), abnormal glucose (n = 201), hypertriglyceridemia (n = 145), hypercholesterolemia (n = 38) and hypertension (n = 34) in 2938 survivors from the St. Jude Lifetime Cohort. A core set of five DNAm sites near CPT1A and LMNA is associated with all CMRFs. Mediation analyses identify 24 sites mediating associations between treatments and CMRFs, implicating inflammatory and metabolic pathways. Notably, cg20370568, a cis-expression quantitative trait methylation site for ANTXR2, mediates 20% of the effect of body-trunk-radiotherapy on abnormal glucose. These findings suggest that prior genotoxic cancer treatments may become biologically embedded through DNAm variations that could contribute to cardiometabolic dysfunction and highlight candidate biomarkers for refining risk stratification and guiding intervention strategies in survivorship care.