Characterization of Somatic Mutations in Air Pollution-Related Lung Cancer.

Abstract

Air pollution has been classified as Group 1 carcinogenic to humans, but the underlying tumorigenesis remains unclear. In Xuanwei City of Yunnan Province, the lung cancer incidence is among the highest in China attributed to severe air pollution generated by combustion of smoky coal, providing a unique opportunity to dissect lung carcinogenesis of air pollution. Here we analyzed the somatic mutations of 164 non-small cell lung cancers (NSCLCs) from Xuanwei and control regions (CR) where smoky coal was not used. Whole genome sequencing revealed a mean of 289 somatic exonic mutations per tumor and the frequent C:G → A:T nucleotide substitutions in Xuanwei NSCLCs. Exome sequencing of 2010 genes showed that Xuanwei and CR NSCLCs had a mean of 68 and 22 mutated genes per tumor, respectively (p < 0.0001). We found 167 genes (including TP53, RYR2, KRAS, CACNA1E) which had significantly higher mutation frequencies in Xuanwei than CR patients, and mutations in most genes in Xuanwei NSCLCs differed from those in CR cases. The mutation rates of 70 genes (e.g., RYR2, MYH3, GPR144, CACNA1E) were associated with patients' lifetime benzo(a)pyrene exposure. This study uncovers the mutation spectrum of air pollution-related lung cancers, and provides evidence for pollution exposure-genomic mutation relationship at a large scale.

• Authors: Xian-Jun Yu, Min-Jun Yang, Bo Zhou, Gui-Zhen Wang, Yun-Chao Huang, Li-Chuan Wu, Xin Cheng, Zhe-Sheng Wen, Jin-Yan Huang, Yun-Dong Zhang, Xiao-Hong Gao, Gao-Feng Li, Shui-Wang He, Zhao-Hui Gu, Liang Ma, Chun-Ming Pan, Ping Wang, Hao-Bin Chen, Zhi-Peng Hong, Xiao-Lu Wang, Wen-Jing Mao, Xiao-Long Jin, Hui Kang, Shu-Ting Chen, Yong-Qiang Zhu, Wen-Yi Gu, Zi Liu, Hui Dong, Lin-Wei Tian, Sai-Juan Chen, Yi Cao, Sheng-Yue Wang, Guang-Biao Zhou
• Journal: EBioMedicine (EBioMedicine) Vol. 2 Issue 6 Pg. 583-90 (Jun 2015) ISSN: 2352-3964 [Print] Netherlands
• PMID: 26288819 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Air Pollutants
• Coal
• Smoke
• Benzo(a)pyrene

Topics

• Aged
• Air Pollutants (adverse effects)
• Air Pollution (adverse effects)
• Base Sequence
• Benzo(a)pyrene (adverse effects)
• Carcinoma, Non-Small-Cell Lung (chemically induced, genetics)
• Cell Transformation, Neoplastic
• Coal (adverse effects)
• Environmental Exposure (adverse effects)
• Female
• Gene Frequency (genetics)
• Genome (genetics)
• Humans
• Lung Neoplasms (chemically induced, genetics)
• Male
• Middle Aged
• Mutation (genetics)
• Mutation Rate
• Sequence Analysis, DNA
• Smoke (adverse effects)