Abstract 112: Transcriptomic changes in the oral mucosal epithelium reflect the physiologic response to indoor burning of solid fuels.

Abstract

Abstract RATIONALE: Human exposure to indoor smoke emissions from the domestic burning of solid fuels (e.g. coal, wood, plant materials) is a major cause of morbidity and mortality that affects nearly half of the world's population. While epidemiologic studies on the health impact of indoor air pollution (IAP) have yielded valuable insights from the use of various exposure assessments (e.g. personal and area air sampling, urinary metabolites), there is a need to connect these exposure measures to biomarkers of the host's physiologic response to exposure. We have previously shown that gene-expression (GE) profiles in the upper airway epithelium are affected by tobacco smoke. Thus, we sought to determine whether transcriptomic changes in the oral mucosal epithelium might also capture physiologic responses to IAP from the burning of solid fuels. METHODS: Buccal mucosa epithelial cell scrapings were collected from healthy, non-smoking female subjects in rural Xuanwei, China, where female lung cancer rates are among the highest in the world. Benzo(a)pyrene (BaP) exposure levels from indoor burning of solid fuels (primarily coal) for cooking and heating were measured by personal in-home air monitoring. RNA from 18 samples was extracted and processed onto Affymetrix Gene 1.0 ST arrays. Student's t-test and DAVID were used to identify and characterize genes that vary between relatively high levels of BaP exposure (n=8; BaP 99.0 +/- 45.9) and low (n=10; BaP 16.2 +/- 6.1) exposure. Using GSEA, results were compared to independent airway epithelial GE profiles that distinguish current smokers from never smokers and bronchial GE profiles in subjects with and without lung cancer. RESULTS: We identified 227 genes that were differentially expressed between subjects with high and low BaP exposure (p<0.01). Genes elevated with high BaP exposure were enriched for genes involved in the activation of apoptosis and the Toll-Like Receptor Signaling pathway. Genes that we have previously shown to have altered expression in the bronchial, buccal, and nasal epithelium of current smokers relative to never smokers were enriched among the genes associated with BaP exposure (GSEA; q<0.01). There was also a significant enrichment for bronchial epithelial airway genes that were altered in subjects with and without lung cancer in a previous report (GSEA; q<0.01). CONCLUSION: Buccal epithelial GE is affected by BaP exposure in a population that uses coal and other solid fuels for indoor cooking and heating among healthy women in Xuanwei, China. Solid fuel emissions may elicit some of the same transcriptomic responses as cigarette smoke and lung cancer. This demonstrates the feasibility of using non-invasively collected buccal GE profiling to assess physiologic responses to other inhaled toxins such as coal smoke in population-based studies. Citation Format: Teresa W. Wang, Qing Lan, Bozena Krystyna, Nathaniel Rothman, Roberta Florido, Wei Hu, Katrina Steiling, Gang Liu, Ji Xiao, Yuriy Alekseyev, Jun Xu, Fusheng Wei, H. Dean Hosgood, Boris Reiss, George Downward, Marc Lenburg, Roel Vermeulen, Avrum Spira. Transcriptomic changes in the oral mucosal epithelium reflect the physiologic response to indoor burning of solid fuels. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 112. doi:10.1158/1538-7445.AM2013-112