Open Access Highly Accessed Research article

Smoking-induced gene expression changes in the bronchial airway are reflected in nasal and buccal epithelium

Sriram Sridhar2, Frank Schembri1, Julie Zeskind4, Vishal Shah4, Adam M Gustafson4, Katrina Steiling1, Gang Liu1, Yves-Martine Dumas1, Xiaohui Zhang1, Jerome S Brody1, Marc E Lenburg134 and Avrum Spira14*

  • * Corresponding author: Avrum Spira

  • † Equal contributors

Author Affiliations

1 Pulmonary Center, Boston University School of Medicine, Albany Street, Boston Massachusetts, USA

2 Pathology Program, Graduate Medical Sciences, Boston University School of Medicine, Albany Street, Boston Massachusetts, USA

3 Department of Genetics and Genomics, Boston University School of Medicine, Albany Street, Boston, MA, USA

4 Bioinformatics Program, Boston University School of Engineering, Cummington Street, Boston Massachusetts, USA

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BMC Genomics 2008, 9:259  doi:10.1186/1471-2164-9-259

Published: 30 May 2008



Cigarette smoking is a leading cause of preventable death and a significant cause of lung cancer and chronic obstructive pulmonary disease. Prior studies have demonstrated that smoking creates a field of molecular injury throughout the airway epithelium exposed to cigarette smoke. We have previously characterized gene expression in the bronchial epithelium of never smokers and identified the gene expression changes that occur in the mainstem bronchus in response to smoking. In this study, we explored relationships in whole-genome gene expression between extrathorcic (buccal and nasal) and intrathoracic (bronchial) epithelium in healthy current and never smokers.


Using genes that have been previously defined as being expressed in the bronchial airway of never smokers (the "normal airway transcriptome"), we found that bronchial and nasal epithelium from non-smokers were most similar in gene expression when compared to other epithelial and nonepithelial tissues, with several antioxidant, detoxification, and structural genes being highly expressed in both the bronchus and nose. Principle component analysis of previously defined smoking-induced genes from the bronchus suggested that smoking had a similar effect on gene expression in nasal epithelium. Gene set enrichment analysis demonstrated that this set of genes was also highly enriched among the genes most altered by smoking in both nasal and buccal epithelial samples. The expression of several detoxification genes was commonly altered by smoking in all three respiratory epithelial tissues, suggesting a common airway-wide response to tobacco exposure.


Our findings support a relationship between gene expression in extra- and intrathoracic airway epithelial cells and extend the concept of a smoking-induced field of injury to epithelial cells that line the mouth and nose. This relationship could potentially be utilized to develop a non-invasive biomarker for tobacco exposure as well as a non-invasive screening or diagnostic tool providing information about individual susceptibility to smoking-induced lung diseases.