Abstract B122: Epigenetic age acceleration and cardiac dysfunction in survivors of adolescent and young adult cancer

Abstract Survivors of adolescent and young adult (AYA) cancer, diagnosed between ages 15-39, are at increased risk for cardiac dysfunction and cardiovascular disease (CVD) due to exposure to cardio-toxic treatments. Epigenetic age clocks, such as Hannum and PCGrimAge, predict biological age and epigenetic age acceleration (EAA) using DNA CpG methylation sites that correlate with chronological age or mortality, respectively. Childhood cancer survivors with a higher EAA have been shown to be at increased risk of CVD; however, this has not been studied in survivors of AYA cancer. Project DANCES (Diversity in Aya caNCEr Survivors) is a retrospective cohort of survivors of AYA cancer treated at MD Anderson between 2000-2016. A total of 374 participants (N=39 Black, 76 Hispanic, 254 White survivors) from Project DANCES with comprehensive clinical data and blood biospecimens available were included in the analysis. DNA methylation profiling was performed and EAA was calculated based on the Hannum and PCGrimAge clocks. Analyses were conducted by patient demographics, timing of the blood draw (pre- or post-treatment), treatment exposures, and CVD diagnosis where there was a median follow-up time of 8.3 years (IQR: 6.05-11.63). A higher EAA is observed in Hispanic and Black survivors compared to White patients (p=0.003, p=0.04, respectively by PCGrimAge). Survivors exposed to chest radiation had a higher EAA than those without chest radiation exposure (p=0.02, Hannum). Patients whose sample was collected post-treatment and who received ≥300mg/m2 anthracyclines had a higher EAA compared to those exposed to lower doses (p=0.0001, PCGrimAge). This increase was similar in White and Hispanic survivors (p=0.0044, p=0.025, respectively by PCGrimAge). Survivors who experienced a CVD event after their blood sample was collected, of all races/ethnicities or when stratified by White or Hispanic patients, had a significantly higher EAA compared to those who did not have a CVD diagnosis (p<0.0001, p=0.001, p=0.02, respectively by PCGrimAge). In a multivariate logarithmic regression analysis, higher EAA is associated with an increased risk of developing a CVD event [OR=1.19, p<0.001, 95% CI: 1.10-1.30]. These findings demonstrate that race/ethnicity and treatment exposure contribute to EAA, and that a higher EAA tends to increase the risk of CVD. Efforts are underway to expand the analysis to additional Black and Hispanic survivors of AYA cancer. Citation Format: Amanda Warner, Amanda Brandt, Qian Xiao, Jian Wang, Greg Aune, Debra Eshelman-Kent, Karen Albritton, Sairah Ahmed, Efstratios Koutroumpakis, Michael E. Roth, Michelle Hildebrandt. Epigenetic age acceleration and cardiac dysfunction in survivors of adolescent and young adult cancer [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr B122.