Abstract B017: Epigenetic age in peripheral blood among children, adolescent, and adult survivors of childhood cancer
Authors: Plonski Noel-Marie , Chen Cheng , Dong Qian , Qin Na , Shelton Kyla C. , Finch Emily , Easton John , Mulder Heather , Zhang Jinghui , Neale Geoffrey , Walker Emily , Wang Hui , Krull Kevin , Ness Kirsten K. , Hudson Melissa M , Robinson Leslie L. , Li Qian , Williams AnnaLynn , Wang Zhaoming 
Published: January 2023

Background: We have previously reported that epigenetic age acceleration (EAA) was associated with prior cancer treatment exposures and certain chronic health conditions (CHCs) among adult survivors of childhood cancer, but the early epigenetic aging pattern among children and adolescent survivors and its implication in CHCs, especially early-onset CHCs, remain to be explored. Methods: Expanded DNAm profiling with EPIC array for survivors in the St. Jude Lifetime Cohort covered the age &lt;20 years (n=690 in a total of 2,846). Epigenetic age (EA) was measured with four epigenetic clocks, i.e., Horvath, Hannum, Levine, and GrimAge. The annual change of EA and EAA were compared in 5 different chronological age groups, i.e., children (0-9 years), adolescent (10-19 years), young adults (20-34 years), middle-aged adults (35-49 years, and old adults (≥50). Logistic regression evaluated the association between EAA and early-onset obesity (&lt;20 years) or severity/burden score of all CHCs. Cox regression assessed the association between EAA and late-mortality. Results: The annual mean change in EA using Horvath and Levine clocks was greatest in children (2.18; 1.63 years) and steadily decreased across age groups with the lowest change in adults ≥50 years (0.53; 0.76 years). However, Hannum and GrimAge clocks showed the greatest annual mean change in young adults (0.76; 0.80 years). Moreover, the Horvath and Levine clocks showed lower EAA in children (-3.57; -0.22) and older adults (-2.34; -1.70) and higher in adolescents (0.92; 1.32) and young adults (1.10; 1.46). Levine and GrimAge clock EAA was significantly associated with increased risk of developing early-onset obesity (Odds Ratio [OR]=1.05, 95% CI=1.01-1.08, p&lt;0.01; OR=1.12, 95% CI=1.03-1.12, p=0.01), increased severity and burden of CHCs (OR=1.02, 95% CI=1.01-1.04, p=0.02; OR=1.04, 95% CI=1.00-1.07, p=0.05)) and late mortality (Hazard Ratio [HR]=1.10, 95% CI=1.05-1.15, p&lt;0.001; HR=1.17, 95% CI=1.10-1.26, p&lt;0.001). Conclusions: Our investigation showed the EAA measured in children and adolescent survivors may be predictive of early-onset CHCs, severity/burden of all CHCs was well as early morality, highlighting that the early start of accelerated aging warrants a need for earlier intervention to prevent morbidity and mortality later in life in childhood cancer survivors. Children and adolescents at elevated aging “trajectory” might benefit greatly from earlier anti-aging interventions including non-pharmacologic (e.g., lifestyle modifications) and pharmacologic (e.g., DNA methylation/demethylating agents) strategies.

Citation Format: Noel-Marie Plonski, Cheng Chen, Qian Dong, Na Qin, Kyla C. Shelton, Emily Finch, John Easton, Heather Mulder, Jinghui Zhang, Geoffrey Neale, Emily Walker, Hui Wang, Kevin Krull, Kirsten K. Ness, Melissa M Hudson, Leslie L. Robinson, Qian Li, AnnaLynn Williams, Zhaoming Wang. Epigenetic age in peripheral blood among children, adolescent, and adult survivors of childhood cancer [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr B017.