Characterization of Somatic Mutations in Air Pollution-Related Lung Cancer.
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.
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China ; School of Life Sciences, University of Science and Technology of China, Hefei 230026, China.
Xian-Jun
XJ
Yu
The Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center, Shanghai 201203, China.
Min-Jun
MJ
Yang
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China.
Bo
B
Zhou
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China.
Gui-Zhen
GZ
Wang
Department of Thoracic Surgery, Yunnan Cancer Hospital, Kunming 650106, China.
Yun-Chao
YC
Huang
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China.
Li-Chuan
LC
Wu
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China.
Xin
X
Cheng
Department of Thoracic Surgery, The Cancer Hospital, Sun Yat-Sen University, Guangzhou 510060, China.
Zhe-Sheng
ZS
Wen
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine, and Shanghai Center for Systems Biomedicine, SJTU, Shanghai 200025, China.
Jin-Yan
JY
Huang
Laboratory of Molecular and Experimental Pathology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
Yun-Dong
YD
Zhang
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China.
Xiao-Hong
XH
Gao
Department of Thoracic Surgery, Yunnan Cancer Hospital, Kunming 650106, China.
Gao-Feng
GF
Li
Laboratory of Molecular and Experimental Pathology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China ; School of Life Sciences, University of Science and Technology of China, Hefei 230026, China.
Shui-Wang
SW
He
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine, and Shanghai Center for Systems Biomedicine, SJTU, Shanghai 200025, China.
Zhao-Hui
ZH
Gu
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China.
Liang
L
Ma
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine, and Shanghai Center for Systems Biomedicine, SJTU, Shanghai 200025, China.
Chun-Ming
CM
Pan
Department of Thoracic Surgery, The First People's Hospital of Yunnan Province, Kunming 650032, China.
Ping
P
Wang
Department of Pathology, The First People's Hospital of Qu Jing City, Qu Jing 655000, Yunnan Province, China.
Hao-Bin
HB
Chen
Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
Zhi-Peng
ZP
Hong
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China.
Xiao-Lu
XL
Wang
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China ; School of Life Sciences, University of Science and Technology of China, Hefei 230026, China.
Wen-Jing
WJ
Mao
Department of Pathology, Rui Jin Hospital Affiliated to SJTU School of Medicine, Shanghai 200025, China.
Xiao-Long
XL
Jin
The Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center, Shanghai 201203, China.
Hui
H
Kang
The Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center, Shanghai 201203, China.
Shu-Ting
ST
Chen
The Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center, Shanghai 201203, China.
Yong-Qiang
YQ
Zhu
The Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center, Shanghai 201203, China.
Wen-Yi
WY
Gu
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China.
Zi
Z
Liu
The Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center, Shanghai 201203, China.
Hui
H
Dong
School of Public Health, The University of Hong Kong, Hong Kong SAR, China.
Lin-Wei
LW
Tian
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University (SJTU) School of Medicine, and Shanghai Center for Systems Biomedicine, SJTU, Shanghai 200025, China.
Sai-Juan
SJ
Chen
Laboratory of Molecular and Experimental Pathology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
Yi
Y
Cao
The Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center, Shanghai 201203, China.
Sheng-Yue
SY
Wang
State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing 100101, China.
Guang-Biao
GB
Zhou
D000368:Aged; D000393:Air Pollutants / Q000009:adverse effects*; D000397:Air Pollution / Q000009:adverse effects*; D001483:Base Sequence; D001564:Benzo(a)pyrene / Q000009:adverse effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000139:chemically induced / Q000235:genetics*; D002471:Cell Transformation, Neoplastic; D003031:Coal / Q000009:adverse effects; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D016678:Genome / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D059645:Mutation Rate; D017422:Sequence Analysis, DNA; D012906:Smoke / Q000009:adverse effects
D000393:Air Pollutants; D003031:Coal; D012906:Smoke; D001564:Benzo(a)pyrene
Air pollution; Exome sequencing; Exposure; Lung cancer; Whole genome sequencing