Abstract 3503: Racial disparity and roles of social determinants of health in epigenetic age acceleration among survivors of childhood cancer
Authors: Plonski Noel-Marie , Chen Cheng , Dong Qian , Qin Na , Song Nan , Easton John , Mulder Heather , Walker Emily , Neale Geoffrey , Zhang Jinghui , Krull Kevin , Ness Kirsten K. , Hudson Melissa M. , Robison Leslie L. , Huang I-Chan , Wang Zhaoming 
Published: April 2023

Abstract
Our published studies demonstrated that epigenetic age acceleration (EAA) is significantly higher in childhood cancer survivors than non-cancer controls. Additionally, EAA is associated with germline genetics, cancer treatments, unfavorable health behaviors, and chronic health conditions. However, our previous studies were limited to non-Hispanic whites (NHW). We aimed to investigate and compare the EAA between non-Hispanic blacks (NHB) and NHW, and evaluate the contribution of social determinants of health (SDOH) to potential racial disparity in EAA. Methylation profiling was generated using Infinium EPIC BeadChips on blood derived DNA from 460 NHB and 2,052 NHW from the St. Jude Lifetime Cohort. EAA was estimated as the residual from the fit of a simple linear regression of epigenetic age (EA, using Levine’s clock) on chronological age (CA, i.e., age at DNA sampling). Cumulative doses of chemotherapy and region-specific radiation exposures were abstracted from medical records. Educational attainment was categorized into 3 levels (&lt; high school, high school, ≥ college). Personal income was categorized into 3 levels (none, &lt; $40,000 and ≥ $40,000). For socioeconomic area deprivation index (ADI), we considered &gt;75th percentile, 40th to 75th percentile, and &lt;40th percentile as high, moderate, and low deprivation, respectively. Multivariable linear regression evaluated associations of EAA with race and SDOH adjusting for sex and cancer treatments. Mediation analysis treated SDOH as mediators, EAA as an outcome, and race as an exposure. The Pearson r between EA and CA was 0.85 and 0.58, and the age slope of EA (i.e., annual change rate of EA) was 1.21 and 0.91, for NHW and NHB, respectively. EAA was much higher in NHB (mean, 5.31; sd, 7.21) than NHW (mean, -1.19; sd, 12.48) with significance in a multivariable regression model adjusting for sex and cancer treatment (NHB vs. NHW: β = 1.90, P = 9.24×10-5). EAA was also associated with educational attainment (high school vs. &lt;high school: β = -2.84, P = 3.22×10-5; college vs. &lt;high school: β = -3.75, P = 2.03×10-7) and ADI (moderate vs. low: β= 1.07, P = 0.026; high vs. low: β = 1.58, P = 2.26×10-3), but not personal income. Notably, after adjusting for SDOH, the association between EAA and race was moderately attenuated (β = 1.50, P = 8.37×10-3). Both educational attainment (15.5%) and ADI (21.4%) mediated the association between race and EAA. We found racial disparity in EAA, with both personal and geographic SDOH as mediators of the association between race and EAA. These data indicate that changes in the social support system at both a personal and community level are needed to reduce socioeconomic disadvantage (e.g., lower education and poor living conditions) and hence the biological aging trajectory. In addition, moderate correlation between EA and CA among NHB suggests that further refined measurement of EA for NHB survivors is needed.
Citation Format: Noel-Marie Plonski, Cheng Chen, Qian Dong, Na Qin, Nan Song, John Easton, Heather Mulder, Emily Walker, Geoffrey Neale, Jinghui Zhang, Kevin Krull, Kirsten K. Ness, Melissa M. Hudson, Leslie L. Robison, I-Chan Huang, Zhaoming Wang. Racial disparity and roles of social determinants of health in epigenetic age acceleration among survivors of childhood cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3503.