Abstract 833: Persistent alterations of gene expression profiling of human peripheral blood mononuclear cells from smokers

Abstract

Abstract The number of validated biomarkers of tobacco smoke exposure is limited, and none exist for tobacco-related cancer. Additional biomarkers for smoke effects on cellular systems in vivo are needed to improve early detection of lung cancer, and to assist the Food and Drug Administration in regulating exposures to tobacco products. We assessed the effects of smoking on the gene expression in vitro and in vivo using human cell cultures and blood from a cross-sectional study. We profiled global transcriptional changes in cultured smokers’ peripheral blood mononuclear cells (PBMCs) treated with cigarette smoke condensate (CSC) in vitro and from well-characterized smokers’ blood (n = 36). ANOVA and linear regression with adjustment for covariates were used for statistical analysis. CSC in vitro altered the expression of 1178 genes (177 genes with > 1.5 fold-change) at P < 0.05. Phase I and II metabolizing enzyme genes were up-regulated, cytokines and chemokines were down-regulated. Nine putative oncogenes and 5 tumor suppressor genes were dysregulated. In vivo, PBMCs of heavy and light smokers differed for 614 genes (29 with > 1.5 fold-change) at P < 0.05 (309 remaining significant after adjustment for age, race and gender). Seventy eight genes had a significant linear correlation (P < 0.01) with cigarettes per day and 28 genes were linearly correlated with cumulative pack-year smoking. Forty-one genes were persistently altered both in vitro and in vivo, 22 having the same expression pattern reported for non-small cell lung cancer. Our data provides evidence that persistent alterations of gene expression in vitro and in vivo may relate to carcinogenic effects of cigarette smoke, and the identified genes may serve as potential biomarkers for cancer. The use of an in vitro model to corroborate results from human studies provides direct evidence for a cause and effect. Citation Format: Daniel Y. Weng, Jinguo Chen, Cenny Taslim, Ping-Ching Hsu, Catalin Marian, Sean P. David, Christopher A. Loffredo, Peter G. Shields. Persistent alterations of gene expression profiling of human peripheral blood mononuclear cells from smokers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 833. doi:10.1158/1538-7445.AM2015-833