Abstract 3187: Genomic Abnormalities in Air Pollution-Related Lung Cancer

The lung cancer incidence in Xuanwei (XW) City and Fuyuan (FY) County in Yunnan Province of China is among the highest in China, owing to high levels of air pollution produced by combustion of smoky coal. This epidemiology profile provides a unique opportunity for identifying the carcinogenic mechanism underlying air pollution. Here, we analyze the genome sequences of 14 XW/FY non-small-cell lung cancers and their paired normal tissues, and report a mean of 289 somatic exonic mutations and 71 genomic rearrangements/tumor. Among the recurring mutated genes, calcium signaling and ion channel genes are the most frequently altered gene category. Higher mutation rate in calcium signaling genes is confirmed by genomic resequencing in 65 XW/FY patients and 85 patients from control regions. Small interfering RNA mediated silencing shows that inactivation of calcium channel leads to inhibition of lung cancer cells, suggesting a role for calcium signaling molecules in air pollution-related carcinogenesis leading to lung cancer. Citation Format: Guang-Biao Zhou, Xian-Jun Yu, Li-Chuan Wu, Yun-Chao Huang, Gao-Feng Li, Zhe-Sheng Wen, Sai-Juan Chen, Yi Cao, Sheng-Yue Wang, Min-Jun Yang, Zhu Chen. Genomic abnormalities in air pollution-related lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3187. doi:10.1158/1538-7445.AM2014-3187