Cardio-oncology & otherCohort study
Epigenetic Age Acceleration Mediates Treatment Effects on Cardiometabolic and Cardiovascular Risk in Childhood Cancer Survivors
- Cohort study with mediation analysis
Authors' conclusion
EAA accounted for a substantial proportion of the association between cancer treatment exposures and risk for CMRFs and cardiovascular diseases.
Study context
- Population
- 5-year childhood cancer survivors from SJLIFE (St. Jude Lifetime Cohort) with DNA methylation profiling
- Participants
- 2,939 survivors
- Exposure
- Cancer treatment exposures, mediated by epigenetic age acceleration
- Outcome
- Proportion of the treatment–outcome association mediated by epigenetic age acceleration (EAA) (DunedinPACE, PCPhenoAge, GrimAge2); outcomes: abnormal glucose metabolism, hypertension, obesity, cardiomyopathy, MI
Main finding
As reported in the abstract
Proportion mediated by EAA
- Abdominal radiotherapy (RT) → abnormal glucose metabolism, DunedinPACE
- 35.4%
- Abdominal RT → abnormal glucose metabolism, GrimAge2
- 16.2%
- Abdominal RT → hypertension, DunedinPACE
- 25.9%
- Anthracyclines → hypertension, DunedinPACE
- 12.5%
- Corticosteroids → obesity, DunedinPACE
- 8.6%
- Heart RT → cardiomyopathy, PCPhenoAge
- 30.3%
- Heart RT → cardiomyopathy, DunedinPACE
- 19.9%
- Heart RT → cardiomyopathy, GrimAge2
- 14.4%
- Heart RT → MI, PCPhenoAge
- 24.1%
- Heart RT → MI, DunedinPACE
- 15.5%
- Heart RT → MI, GrimAge2
- 13.2%
- Anthracyclines → cardiomyopathy, GrimAge2
- 6.0%
- Anthracyclines → cardiomyopathy, PCPhenoAge
- 5.2%
- Anthracyclines → cardiomyopathy, DunedinPACE
- 3.9%
Observational data: associations, not effects.
Original publication
Epigenetic Age Acceleration Mediates Treatment Effects on Cardiometabolic and Cardiovascular Risk in Childhood Cancer Survivors. JACC CardioOncol. Published 21 June 2025. doi:10.1016/j.jaccao.2025.06.001
Summarised from the published abstract; every number is checked against it