Dataset Information

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.

SUBMITTER: Yu XJ

PROVIDER: S-EPMC4534757 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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

Yu Xian-Jun XJ Yang Min-Jun MJ Zhou Bo B Wang Gui-Zhen GZ Huang Yun-Chao YC Wu Li-Chuan LC Cheng Xin X Wen Zhe-Sheng ZS Huang Jin-Yan JY Zhang Yun-Dong YD Gao Xiao-Hong XH Li Gao-Feng GF He Shui-Wang SW Gu Zhao-Hui ZH Ma Liang L Pan Chun-Ming CM Wang Ping P Chen Hao-Bin HB Hong Zhi-Peng ZP Wang Xiao-Lu XL Mao Wen-Jing WJ Jin Xiao-Long XL Kang Hui H Chen Shu-Ting ST Zhu Yong-Qiang YQ Gu Wen-Yi WY Liu Zi Z Dong Hui H Tian Lin-Wei LW Chen Sai-Juan SJ Cao Yi Y Wang Sheng-Yue SY Zhou Guang-Biao GB

EBioMedicine 20150407 6

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 co ...[more]

PMID: 26288819

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Project description:ObjectiveLung cancer is a leading cause of cancer death in the United States. Exposure to outdoor air pollution (OAP) is associated with increased lung cancer incidence, however little is known about the association of OAP and survival after diagnosis.MethodsWe investigated the effects of OAP and lung cancer survival in Pennsylvania using data from Pennsylvania Cancer Registry. The study population consisted of 252,123 patients diagnosed between 1990 and 2017. The Environmental Protection Agency's ambient air monitoring network provided information on OAP exposure of NO2, O3, PM2.5, and PM10. Mean OAP exposures were calculated by interpolating exposure concentrations from the five nearest monitors within a 50-kilometer radius of each patient's residential address from date of diagnosis to date of death or last contact. Cox proportional-hazards models were used to estimate the hazard ratios (HR) for OAP exposures for overall and lung cancer-specific survival. Statistical analyses were stratified by SEER cancer stage groupings (localized, regional, and distant) and adjusted for individual-level and area-level covariates.ResultsMedian survival time was 0.76 [CIs: 0.75, 0.77] years for the study population and for localized, regional, and distant site diagnosis were 2.2 [CIs: 2.17, 2.23], 1.13 [CIs: 1.12, 1.15], and 0.42 [CIs: 0.41, 0.43] years, respectively. NO2 indicated the greatest HR which increased with increasing magnitude of exposure across all cancer staging groups for deaths before 2-years post-diagnosis. HRs varied by stage and magnitude of OAP exposure with greatest overall effects shown in NO2 followed by PM2.5, O3, and PM10. A subgroup analysis of patients with treatment status information (2010-2017) showed similar associations of increasing HRs with increasing exposure.ConclusionThese findings supported the hypotheses that OAP can influence the carcinogenic process, impairing chemotherapy treatment, and provide important public health implications since environmental factors are not often considered in prognosis of survival after diagnosis.

Project description:IntroductionCommuting exposes millions of people to carcinogens from traffic-related air pollution (TRAP) but is seldomly considered in epidemiologic studies of lung cancer. In the prospective United Kingdom (UK) Biobank cohort study, we investigated associations between commute patterns, residential nitrogen dioxide concentrations (NO2; a surrogate for TRAP), and lung cancer risk.MethodsWe analyzed 234,124 employed participants at baseline (2006-2010). There were 493 incident lung cancer cases diagnosed over an average 7-year follow-up. Subjects were cross-classified into exclusive categories of commute mode (automobile, public transportation, walking, cycling, active mixture, and other mixture) and frequency (regular: 1-4, often: ≥5 work-bound trips/week). Annual average residential NO2 concentrations in 2005-2007 were estimated with land use regression. Multivariable Cox regression was used to estimate associations between commute patterns, NO2 quartiles, and incident lung cancer. We conducted analyses stratified by NO2 (>, ≤median = 28.3 µg/m3) and potential confounders such as sex and smoking.ResultsCompared to regular automobile use, commuting often by public transportation was associated with increased lung cancer risk (hazard ratio (HR) = 1.58, 95% confidence intervals (CI):1.08-2.33). Additionally, we found a positive exposure-response relationship with residential NO2 (HRQ2 = 1.21, 95 %CI: 0.90-1.62; HRQ3 = 1.48, 95 %CI: 1.10-1.99; HRQ4 = 1.58, 95 %CI: 1.13-2.23; p-trend = 3.1 × 10-3). The public transportation association was observed among those with higher NO2 (p-interaction = 0.02). Other commute categories were not associated with risk.ConclusionsCommuters residing in high-NO2 areas who often use public transportation could have elevated lung cancer risk compared to regular automobile users. These results warrant investigations into which component(s) of public transportation contribute to the observed association with increased lung cancer risk.

Dataset Information

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

Publications

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

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