Abstract

Although the most important risk factor for lung cancer is smoking, lung cancer in never smokers (LCINS) is being increasingly reported. Thus, studies of other risk factors for lung cancer are needed. Recently, radon (Rn), a natural, noble gas, was recognized as the second most common risk factor for lung cancer. OBJECTIVES To identify variations in genes associated with lung cancer in never smokers exposed to radon gas. We conducted an optimized next generation sequencing analysis of lung cancer-related genes in normal and tumor tissues from Korean LCINS patients who had been exposed to radon gas indoors. A total of 926 SNPs showing genome-wide statistical significance were analyzed. Several genes commonly associated with lung cancer, EGFR and TP53 in chromosomes 7 and 17, respectively, showed significant correlations with LCINS. Others included ERG in chromosome 21, RIT1 in chromosome 1, and BIRC6 in chromosome 2. Meanwhile, several additional loci showed novel associations with LCINS as a result of exposure to radon gas, including PDK1, VHL, WHSC1L1, CHD4, MBD2, ATRX, CCND1, and PTPRD. Using next generation sequencing, we found several lung cancer-related genes to be associated with tumors in never smokers exposed to radon. Most of the noted loci have not been shown to be associated with lung cancer, and provide new insights into the development of LCINS. Our findings may serve as a reference for replication and validation studies on the prevention and treatment of LCINS as a result of exposure to radon gas. ACKNOWLEDGMENTS: This study was supported by the Korean Ministry of Environment as part of the “Environmental Health Action Program” (grant number 2015001350002).

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