Abstract 3233: The effects of electronic cigarette exposure on genome-wide expression in human bronchial epithelium
Authors: Weng Daniel Y. , Song Min-Ae , Brasky Theodore M. , McElroy Joseph P. , Mathe Ewy , Freudenheim Jo L. , Wewers Mark D. , Shields Peter G. 
Published: August 2018

Abstract
Background: Although smoking rates continue to decline in US adults, the number of electronic cigarette (e-cig) users is rapidly growing, especially among youth. Exposure to cigarette smoke is known to result in lung cancer and chronic obstructive pulmonary disease, is associated with inflammatory and immune responses generally, and effects gene expression related these and other pathways. However, the effects of e-cigs on the gene expression and inflammation in the bronchial epithelium are largely unknown. We conducted a cross-sectional study to evaluate the effects of e-cig use on gene expression in the bronchial epithelium, in comparison to effects on never smokers and cigarette smokers.
Methods: Epithelia brushings were obtained by bronchoscopy from never smokers (n=42), e-cig users (n=14), and current smokers (n=16) (overall, age 21-30, 78% European-American, 54% male). RNA was extracted and profiled for the whole genome transcriptome (Affymetrix Human Transcriptome Array 2.0). Between group differences were determined with the t-test. False Discovery Rate (FDR) &lt; 0.05 was considered significant. Functional and network analyses were performed using Ingenuity Pathway Analysis (IPA) software.
Results: The average number of cigarettes smoked per day in the smoker group was 16, ranging from 10 to 20 cigarettes/day. In the e-cig user group, the average number of puffs inhaled per day was 173, ranging from 20 to 600, and the average volume of e-liquid per day was 8 ml, ranging from 2 to 20 ml. Of the 14 e-cig users, eleven identified themselves as former smokers (average 24 months since last cigarette), while three were never-smokers. In microarray analysis, comparing never smoker and smoker groups, there were 2,536 differentially expressed genes (DEGs; 1,235 up-regulated genes, 1,301 down-regulated genes in smokers) and 69 DEGs comparing never smoker and e-cig user groups (59 up-regulated genes, 10 down-regulated genes in e-cig users). In addition, there were 108 DEGs between e-cig user and smoker groups (83 up-regulated genes, 25 down-regulated genes in smokers). Several well-known smoking-related genes such as CYP1B1, AKR1B10, ALDH3A1, CYP2A13, and CX3CL1 were significantly decreased in their expression for e-cig users compared to smokers. Unsupervised hierarchical clustering revealed that the expression profiles of never smokers and e-cig users are more similar to each other compared to profiles of smokers. Pathway analysis of smoking-related genes revealed that NRF2-mediated oxidative stress was the most significant canonical pathway (P = 7.88E-11).
Conclusions: Consistent with the hypothesis that e-cigs are less harmful than smoking, bronchial epithelium gene expression profiles of never smokers and e-cig users are more similar, while smokers exhibit distinct profiles. Associations of different nicotine products are apparent in gene expression profiles.
Citation Format: Daniel Y. Weng, Min-Ae Song, Theodore M. Brasky, Joseph P. McElroy, Ewy Mathe, Jo L. Freudenheim, Mark D. Wewers, Peter G. Shields. The effects of electronic cigarette exposure on genome-wide expression in human bronchial epithelium [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3233.