Abstract 2309: Exposure to solid fuel burning and transcriptomic changes in the nasal epithelium in never smoking women in Guatemala

Abstract Introduction Understanding environmental-exposure associated gene expression alterations provides insights into how they contribute to cancer risk. We previously showed that individuals exposed to diesel engine exhaust (DEE) or smoky coal exhibit gene expression changes overlapping with those of smokers, suggesting shared mechanisms of toxicity. Wood smoke, produced by incomplete combustion of biomass fuels, is classified as probably carcinogenic (Group 2A), yet studies of its gene expression effects are limited. Here, we conducted a pilot study to examine whether genes associated with smoking, DEE, and smoky coal exposure are also differentially expressed in individuals exposed to wood smoke. Methods We studied 16 never-smoking women from Guatemala in the Household Air Pollution Intervention Network trial who use wood as their primary fuel. PM2.5 exposure was measured with monitors, and urinary 1-Hydroxypyrene (1-OHP) was assessed as a biomarker of polycyclic aromatic hydrocarbons exposure. Nasal turbinate brush samples underwent bulk RNA-seq and were processed via a GTEx-based pipeline. Differential expression (DE) analysis to compare high vs. low PM2.5 and 1-OHP was conducted using limma. Gene Set Enrichment Analysis was used to evaluate whether previously reported gene signatures associated with smoking, DEE exposure, and smoky coal use, were enriched among genes up- and down-regulated for each exposure, ranked by t-statistics. Results We found that both up-regulated and down-regulated smoking-associated signatures were concordantly enriched in wood smoke exposed women with high levels of PM2.5 (p = 0.001 and p=0.04, respectively) and among women with elevated 1-OHP levels (p 0.001 and p = 0.015, respectively). Genes down-regulated with exposure to smoky coal and DEE were also suppressed in participants with high levels of PM2.5 (p=0.005 for smoky coal signature) and 1-OHP (p0.001 Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2309.