Abstract 4219: Smoky coal exposure is associated with epigenetic accelerated aging

Abstract Household air pollution (HAP) from indoor combustion of solid fuel is a global health burden that has been linked to lung cancer. A striking example occurs in Xuanwei, China where the lung cancer rate for never smoking women is among the highest in the world and largely attributed to high levels of various toxic constituents, including polycyclic aromatic hydrocarbons (PAHs), a combustion product of smoky (bituminous) coal used for cooking and heating. Several air pollution constituents have been associated with epigenetic accelerated aging (EAA) derived from DNA methylation (DNAm)-based biomarkers that are highly correlated with biological processes underlying aging-related diseases. We aim to assess the association between HAP exposure and EAA in Xuanwei, China. We analyzed 106 never smoking women in an exposure assessment study in Xuanwei, China with a repeat DNA sample from 23 subjects. Household fuel type used for cooking and heating (smoky vs. smokeless coal) was collected using a questionnaire, and exposure models were used to predict levels of 43 individual HAP constituents for current and childhood exposure. Leukocyte DNAm was measured using Illumina EPIC array. EAA was derived for five clocks using the Horvath calculator and defined as the residuals resulting from regressing each clock on chronological age. We used generalized estimating equations to assess the associations between fuel type, clusters derived from predicted levels of HAP exposure, and ambient 5-methylchrysene (5-MC), a carcinogenic PAH previously associated with lung cancer in Xuanwei and selected a priori for analyses, as independent variables and EAA clocks as dependent variables, while accounting for repeated-measurements. We observed a significant increase in GrimAge EAA among smoky coal users compared to smokeless coal users for current (β=1.84 years (y), 95% confidence interval (CI): 0.59, 3.09, P-value=0.004) and childhood (β=4.14 y, 95% CI: 1.63, 6.64, P-value=0.001) exposures. We also observed a monotonic increase in GrimAge EAA for a cluster of 31 PAHs reflecting current exposure (β=0.77 y, 95% CI: 0.36, 1.19, P-value=3 × 10−4) and for a cluster of 33 PAHs reflecting childhood exposure (β=0.92 y, 95% CI: 0.40, 1.45, P-value=0.001). Ambient 5-MC, one of the constituents within the PAH clusters, was found to have an increasing monotonic relationship with GrimAge EAA for current (β=0.15 y, 95% CI: 0.05, 0.25, P-value=0.003) and childhood (β=0.30 y, 95% CI: 0.13, 0.47, P-value=4.7 × 10−4) exposures. Our findings suggest that exposure to PAH from indoor smoky coal combustion is associated with EAA, particularly for the GrimAge clock, a strong biomarker of mortality. This finding is consistent with our recent observation linking accelerated GrimAge to increased risk of lung cancer in a prospective study of never smoking women in China. Additionally, our study provides further support for 5-MC as a prominent carcinogenic component of smoky coal emissions. Citation Format: Batel Blechter, Andres Cardenas, Seraphina (Junming) Shi, Mohammad L. Rahman, Jason Y.Y. Wong, Wei Hu, George S. Downward, Lutzen Portengen, Richard Cawthon, H. Dean Hosgood, Jihua Li, Debra T. Silverman, Yunchao Huang, Roel Vermeulen, Nathaniel Rothman, Qing Lan. Smoky coal exposure is associated with epigenetic accelerated aging. [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 4219.