Abstract B017: Epigenetic age in peripheral blood among children, adolescent, and adult survivors of childhood cancer

Abstract

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 <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 (<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<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<0.001; HR=1.17, 95% CI=1.10-1.26, p<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.

Current evidence supporting associations of DNA methylation measurements with survivorship burdens in cancer survivors: A scoping review

“…In total, 22 studies were discovered meeting inclusion criteria for this review (Table S3). 19,40–60 …”

Deficit Accumulation Index and Biological Markers of Aging in Survivors of Childhood Cancer

“…A previous study reported that EAA based on DNAm PhenoAge was associated with specific cancer treatment exposures and chronic health conditions 16 and found different cross-sectional patterns of DNAm PhenoAge across chronological age-defined groups. 24 We derived the EAA by calculating the residual for each individual based on the least-squares regression of estimated DNAm PhenoAge against chronological age at blood draw for DNA sampling. The WGS data were generated using the HiSeq X Ten System (Illumina).…”

Utilizing epigenetics to study the shared nature of development and biological aging across the lifespan

“…There is a notable lack of studies examining the longitudinal stability and change of MPSs in early childhood, because repeated measurements of DNA methylation in young children are still rare and the idea to examine biological aging in children is relatively new. Similarly, very few studies have explored the clinical relevance of MPSs in pediatric cohorts, though there is some evidence to suggest that they may, for example, help identify survivors of childhood cancer at increased risk for early-onset obesity, morbidity, and mortality 37 .…”