Air pollution-related lung cancer has been considered as an exacerbating public health problem worldwide. For instance, Xuanwei and Fuyuan County in Yunnan Province in China are heavily air-polluted regions with exceptionally high lung cancer rates. Hence, these regions can be used as very good models to study air pollution-related lung cancer.In cancer, changes in driver genes are crucial to carcinogenesis. Clinically, patients with specific genetic alterations exhibit higher sensitivity to targeted therapy than to other therapeutic strategies. This study mainly aimed to define the status of clinically significant oncogenes in air pollution-related lung cancers and to establish a simple and sensitive test to screen patients with particular genetic changes.
82 tissue samples of lung cancer and adjacent nonmalignant lung tissues were obtained from patients in Xuanwei and Fuyuan. These tissue samples and 13 cell lines were analyzed through the combined reverse transcription PCR and DNA sequencing to determine the expression and gene mutation of HER2 and BRAF. These tissue samples and cell lines were also examined through RT-PCR to identify the incidence of two fusion genes, namely EML4-ALK and CD74-ROS1.
Of the 82 patients with non-small cell lung cancer, 20.7% (17/82) exhibited HER2 upregulation, 1.21% (1/82) harbored HER2 insertion mutation at exon 20 and 6.1% (5/82) showed ALK gene rearrangements. Of the 5 cases with the gene rearrangements, two belonged to EML4-E2 + ALK-E20 and three were EML4-E13 + ALK-E20. Of the 82 patients, 3.6% (3/82) carried the ROS1 fusion gene with CD74 (CD74-E6 + ROS1-E34).
The overexpression and mutation of HER2, EML4-ALK and CD74-ROS1 were observed in patients living in highly air-polluted regions such as Xuanwei and Fuyuan. These genetic alterations may participate in air pollution-induced lung carcinogenesis. The HER2 overexpression and the EML4-ALK fusion are molecular targets of personalized therapy. To guide treatments, we should screen these genetic alterations in air pollution-related lung cancers through various methods such as an RT-PCR-based test. This test is indeed a useful tool to screen these genetic alterations in clinical applications.
Clinical trial identification
RT-PCR-based test is indeed a useful tool to screen these genetic alterations in clinical applications.
All authors have declared no conflicts of interest.