Abstract 2354: Nasal gene expression reflects the physiologic response to potentially reduced exposure products
Authors: Hijazi Kahkeshan , Bomalysz Bozena , Steiling Katrina , Xiao Ji , Liu Gang , Alekseyev Yuriy , Yves Martine Dumas , Hertsgaard Louise A. , Jensen Joni , Vogel Rachel Isaksson , Hatsukami Dorothy , O'Connor George , Brooks Daniel R. , Beane Jennifer , Spira Avrum 
Published: May 2015

Abstract
Rationale
Potentially reduced exposure products (PREPs) are tobacco-based products that may yield lower toxicant levels as compared to traditional cigarettes thereby possibly mitigating tobacco-exposure related harm. Due to their increasing popularity, there is an urgent need to develop approaches for evaluating the biological impact of these products to determine their potential health risks. We have shown that gene expression profiling of intra- and extra-thoracic airway epithelium can serve as an indicator of physiological responses to cigarette smoke exposure. Our goal here is to establish whether this same approach might identify similarities and differences in the response to reduced exposure tobacco products. We therefore examined longitudinal gene-expression alterations upon switching from traditional cigarettes to a lower nicotine product (Xodus) in readily collected nasal epithelium and compared these transcriptomic alterations to those associated with smoking-cessation.
Methods
Nasal epithelial brushings were obtained from 13 active smokers who switched to Xodus cigarettes for 6 weeks and then were tobacco abstinent for the next 18 weeks. Nasal brushings were obtained at baseline and at 4, 6, 16, and 24-weeks. Alveolar carbon monoxide levels were used to confirm cigarette use at baseline, 4 and 6 weeks and tobacco abstinence at 16 and 24 weeks. RNA from the nasal brushings was processed and hybridized to Affymetrix Human Gene 1.0 ST Arrays. Gene expression alterations at each time point were identified using a mixed model ANOVA.
Results
Alterations in the expression levels of 161 genes were associated with either switching to PREPs or with complete smoking cessation (FDR&lt;0.2). For a minority of genes, Xodus usage resulted in decreased expression levels that further decreased upon smoking cessation. These genes were primarily involved in xenobiotic metabolism (P&lt;0.05). The majority of genes altered by smoking cessation time points do not change upon switching to this PREP product.
Conclusion
Our data indicate that some of the gene expression differences induced by switching to the PREP product are intermediate between traditional cigarette smoking and tobacco abstinence whereas majority of gene expression remain unaltered with Xodus use. These data suggest that the PREP product may only constitute partially reduced exposure. Our study further suggests that the nasal epithelium can serve as a minimally invasive tool to measure responses to alternative tobacco products and may ultimately serve as a biomarker to evaluate the potential disease risks associated with these products.
Citation Format: Kahkeshan Hijazi, Bozena Bomalysz, Katrina Steiling, Ji Xiao, Gang Liu, Yuriy Alekseyev, Martine Dumas Yves, Louise A. Hertsgaard, Joni Jensen, Rachel Isaksson Vogel, Dorothy Hatsukami, George O'Connor, Daniel R. Brooks, Jennifer Beane, Avrum Spira. Nasal gene expression reflects the physiologic response to potentially reduced exposure products. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2354. doi:10.1158/1538-7445.AM2014-2354