Screening of significant oncogenic changes in air pollution-related lung cancer in Chinese population

Background: Air pollution-related lung cancer has been considered as a deteriorating public health problem worldwide, particularly in developing countries. The highly air polluted regions in China particularly Xuanwei and Fuyuan counties have markedly high lung cancer rates and are considered as good models to study air pollution-related lung cancer. The present study investigated the clinically significant oncogenes in air pollution-related lung cancers. Methods: A combination of reverse transcriptase PCR (RT-PCR) and DNA sequencing was applied to examine the expression, mutations, or fusions of target genes, including human epidermal growth factor receptor 2 (HER2), echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), and cluster of differentiation 74-ROS proto-oncogene 1 (CD74-ROS1). Results: Of the 82 patients with lung cancer, 20.7% (17/82) exhibited HER2 up-regulation, and 1.2% (1/82) harbored HER2 insertion at exon 20. HER2 overexpression was not associated with air pollution levels and smoking status. A total of 6.1% (5/82) samples exhibited ALK gene rearrangements; two belonged to EML4-E2 + ALK-E20 and three were EML4-E13 + ALK-E20; all the five cases occurred either in smokers or in patients from the most air-polluted region. A total of 3.6% (3/82) carried the CD74-ROS1 fusion gene (CD74-E6 + ROS1-E34); the fusion event was not statistically associated with air pollution levels. Conclusions: The high rates of prevalence indicated in the present study suggest that the screening of HER2 overexpression and EML4-ALK fusion events may assist in guiding treatment in air pollution-related lung cancer; the RT-PCR-based test proposed in this study may be a useful tool in clinical applications to screen these genetic changes.