Smoke-induced and COPD-related epithelial gene expression profiles: relationship with lung cancer

1730 Rationale:
 Cigarette smoking is the main risk factor for both development of squamous cell lung carcinoma (SCC) and chronic obstructive pulmonary disease (COPD). Additionally, COPD itself is an independent risk factor for SCC. This suggests a common genetic background of COPD and SCC.
 Objectives:
 To analyze smoke-induced and COPD-related gene expression changes in histologically normal bronchial epithelium and compare the expression levels of the differentially expressed genes to the levels in SCC.
 Methods:
 Gene expression profiles were generated using Agilent whole human genome microarray for 28 laser microdissected bronchus epithelial samples of current and ex-smokers from patients with and without COPD, and 35 laser microdissected SCC samples.
 Results:
 Gene expression analysis revealed 246 genes that were significantly different between current and ex-smokers, independent of smoking history. Despite the important role of epithelium in pathogenesis of COPD we found no significant differences in gene expression levels between individuals with and without COPD. To assess whether an association exists between the 246 smoking related differentially expressed genes and SCC, we compared these expression levels with those in the SCC samples. Genes that were upregulated in current smokers, mainly related to oxidative stress response, showed similar expression levels in SCC. Interestingly, the downregulated genes in current smokers including several tumor suppressor genes showed a further reduction in expression levels in SCC.
 Conclusions:
 This is the first study that demonstrated persistence or even enhancement of smoke-induced genetic changes in SCC, indicating a role in early genetic changes in SCC oncogenesis.