Abstract 7441: Health-Related quality of life and DNA methylation-based aging biomarkers among survivors of childhood cancer: Results from the St. Jude Lifetime Cohort

Abstract Background: Childhood cancer survivors often reported poorer health-related quality-of-life (HRQOL) compared to age/sex-matched controls, indicating toxic stress resulting from high burden of treatment-related late effects. This study aimed to investigate cross-sectional associations between poorer HRQOL and epigenetic age acceleration (EAA) using several epigenetic clocks as well as other DNA methylation (DNAm) -based aging biomarkers. Methods: DNAm was generated using the Infinium EPIC BeadChip version 1 with blood-derived DNA (median min-max for age at blood draw = 34. 5 18. 5-66. 6 years) from 2, 206 long-term survivors in the St. Jude Lifetime Cohort. DNAm-based aging biomarkers and epigenetic age using multiple clocks (e. g. , GrimAge; DNAmB2M: beta-2-microglobulin; DNAmADM: adrenomedullin) were derived from the DNAm Age Calculator (https: //dnamage. genetics. ucla. edu). HRQOL was measured using the Medical Outcomes Study 36-Item Short-Form Health Survey which assesses eight domains, and physical (PCS) and mental (MCS) component summaries. General linear models evaluated associations between HRQOL and epigenetic age acceleration (EAA, e. g. , EAAGrimAge) or other DNAm-based biomarkers (e. g. , chronological age adjusted residuals of DNAmB2M, which was similar to the approach in which EAA was derived) after adjusting for age, sex and cancer treatment exposures. Results: Worse physical and mental HRQOL was associated with greater EAAGrimAge (PCS: β 95%CI=-0. 621 -0. 744, -0. 499 years, P=2. 48 × 10−21; MCS: -0. 548 -0. 667, -0. 430 years, P=2. 82 × 10−18; and all eight individual HRQOL domains), followed by chronological age adjusted residuals of DNAmB2M (PCS: -0. 101-0. 144, -0. 058, P=2. 31 × 10−5; MCS: (-0. 053 -0. 094, -0. 011, P=0. 030; and seven HRQOL domains), and chronological age adjusted residuals of DNAmADM (PCS: -0. 096 -0. 139, -0. 053, P=5. 45 × 10−5; and five HRQOL domains). EAAHorvath (Horvath clock, the representative 1st generation epigenetic clock) was the least informative biomarker, which was not associated with any HRQOL domains. Conclusions: Worse HRQOL in different domains was associated with EAAGrimAge and chronological age adjusted residuals of DNAmB2M, although future longitudinal studies are needed to illuminate the cause and consequence relationship between HRQOL and aging biomarkers. Citation Format: Noel-Marie Plonski, Yue Pan, Cheng Chen, Qian Dong, Xijun Zhang, Nan Song, Kyla Shelton, John Easton, Heather Mulder, Jinghui Zhang, Geoffrey Neale, Emily Walker, Hui Wang, Rachel Webster, Tara Brinkman, Kevin R. Krull, Gregory T. Armstrong, Kirsten K. Ness, Melissa M. Hudson, Qin Li, I-Chan Huang, Zhaoming Wang. Health-Related quality of life and DNA methylation-based aging biomarkers among survivors of childhood cancer: Results from the St. Jude Lifetime Cohort abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 7441.