Evidence mapPaperPMID 40624951Full record

ArticleJACC. CardioOncology2025

Epigenetic Age Acceleration Mediates Treatment Effects on Cardiometabolic and Cardiovascular Risk in Childhood Cancer Survivors.

Xiaoxi Meng, Tiffany Eulalio, Yoonji Kim, John Easton, Heather L Mulder, Emily Walker, Geoffrey Neale, Nan Song, Kyla Shelton, Rebecca M Howell and 9 more

Abstract read
In one paragraph

Article in JACC. CardioOncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Article
  2. Cancer Treatment-Related Cardiotoxicity among Survivors of Childhood Cancer: A Comparative and Integrated View of Multiple Measures of Biological Age Acceleration.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026
    Article
  3. Review
  4. Article
  5. Article
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Xiaoxi MengDepartment of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Tiffany EulalioDepartment of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Yoonji KimDepartment of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
John EastonDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Heather L MulderDepartment of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Emily WalkerHartwell Center, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Geoffrey NealeHartwell Center, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Nan SongCollege of Pharmacy, Chungbuk National University, Cheongju, Korea.
Kyla SheltonDepartment of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Rebecca M HowellDivision of Radiation Oncology, Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Mengqi XingDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Sedigheh MirzaeiDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Deo Kumar SrivastavaDepartment of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Bonnie KyDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Stephanie B DixonDepartment of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee, USA; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Melissa M HudsonDepartment of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee, USA; Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Kirsten K NessDepartment of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Gregory T ArmstrongDepartment of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Zhaoming WangDepartment of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee, USA; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA. Electronic address: zhaoming.wang@stjude.org.

Funding

ST JUDE CHILDRENS CANCER CENTER SUPPORT GRANT (CCSG)P30CA021765 · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 1985 to 2025
$34.0M
Trajectory of epigenetic aging and health outcomes in childhood cancer survivorsR01CA279520 · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2025 to 2025
$755k
Genomics-based Mechanistic Investigation of Cancer-treatment Related Cardiotoxicity among Survivors of Childhood CancerR01CA290112 · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · 2025 to 2025
$690k
NCI NIH HHS P30 CA021765NCI NIH HHS R01 CA279520NCI NIH HHS R01 CA290112NCI NIH HHS U01 CA195547
6 · The paper itself

Abstract

backgroundChildhood cancer survivors are at increased risk for epigenetic age acceleration (EAA) and subsequent morbidities, including cardiometabolic risk factors (CMRFs) and cardiovascular diseases, because of prior genotoxic treatments.

objectivesThe aim of this study was to evaluate the mediating role of EAA in the relationship between cancer treatment exposures and risk for CMRFs and cardiovascular diseases.

methodsThis study included 2,939 5-year survivors from SJLIFE (St. Jude Lifetime Cohort) who underwent DNA methylation profiling using peripheral blood mononuclear cells. EAA was calculated using 3 established epigenetic clocks: DunedinPACE, PCPhenoAge, and GrimAge2. Treatment data, including body region-specific radiotherapy (RT) and chemotherapeutic agents such as anthracyclines and corticosteroids, were abstracted from medical records. Outcomes included 3 CMRFs (abnormal glucose metabolism, hypertension, and obesity) and 2 cardiovascular diseases (cardiomyopathy and myocardial infarction). Mediation analysis was conducted to quantify the extent to which EAA mediated the association between each treatment exposure and each clinical outcome.

resultsEAA partially mediated the associations between abdominal RT and abnormal glucose metabolism (DunedinPACE 35.4%, GrimAge2 16.2%), between abdominal RT (DunedinPACE 25.9%) or anthracyclines (DunedinPACE 12.5%) and hypertension, and between corticosteroids and obesity (DunedinPACE 8.6%). EAA also mediated the associations between heart RT and cardiomyopathy (PCPhenoAge 30.3%, DunedinPACE 19.9%, GrimAge2 14.4%) and myocardial infarction (PCPhenoAge 24.1%, DunedinPACE 15.5%, GrimAge2 13.2%), and anthracyclines and cardiomyopathy (GrimAge2 6.0%, PCPhenoAge 5.2%, DunedinPACE 3.9%).

conclusionsEAA accounted for a substantial proportion of the association between cancer treatment exposures and risk for CMRFs and cardiovascular diseases. These findings provide insight into biological aging as a potential mechanistic pathway and support the development of interventions targeting accelerated aging to mitigate long-term treatment-related toxicities and reduce premature mortality in this high-risk population.

Indexed as

biomarkerscancer survivorshipcancer treatmentcardiometabolic risk factorscardiovascular diseaseschildhood cancer survivorepidemiologyepigenetic age accelerationepigeneticsmediationpreventiontreatment

Identifiers

PMID40624951
PMCPMC12790056

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.