Genomic evidence of lung carcinogenesis associated with coal smoke in Xuanwei area, China.
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ABSTRACT:
SUBMITTER: Zhang H
PROVIDER: S-EPMC8692936 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesLung cancer rates in Xuanwei are the highest in China. In-home use of smoky coal has been associated with lung cancer risk, and the association of smoking and lung cancer risk strengthened after stove improvement. Here, we explored the differential association of tobacco use and lung cancer risk by the intensity, duration, and type of coal used.Materials and methodsWe conducted a population-based case-control study of 260 male lung cancer cases and 260 age-matched male controls. Odds ratios (OR) and 95% confidence interval (CI) for tobacco use was calculated by conditional logistic regression.ResultsUse of smoky coal was significantly associated with an increased risk of lung cancer, and tobacco use was weakly and non-significantly associated with lung cancer risk. When the association was assessed by coal use, the cigarette-lung cancer risk association was null in hazardous coal users and elevated in less hazardous smoky coal users and non-smoky coal users. The risk of lung cancer per cigarette per day decreased as annual use of coal increased (>0-3 tons: OR: 1.09; 95% CI: 1.03-1.17; >3 tons: OR: 0.99; 95% CI: 0.95-1.03). Among more hazardous coal users, attenuation occurred at even low levels of usage (>0-3 tons: OR: 1.02; 95% CI: 0.91-1.14; >3 tons: OR: 0.94; 95% CI: 0.97-1.03).ConclusionWe found evidence that smoky coal attenuated the tobacco and lung cancer risk association in males that lived in Xuanwei, particularly among users of hazardous coal where even low levels of smoky coal attenuated the association. Our results suggest that the adverse effects of tobacco may become more apparent as China's population continues to switch to cleaner fuels for the home, underscoring the urgent need for smoking cessation in China and elsewhere.
| S-EPMC3967129 | biostudies-literature
Project description:ObjectiveTo estimate the risk of lung cancer associated with the use of different types of coal for household cooking and heating.SettingXuanwei County, Yunnan Province, China.DesignRetrospective cohort study (follow-up 1976-96) comparing mortality from lung cancer between lifelong users of "smoky coal" (bituminous) and "smokeless coal" (anthracite).Participants27,310 individuals using smoky coal and 9962 individuals using smokeless coal during their entire life.Main outcome measuresPrimary outcomes were absolute and relative risk of death from lung cancer among users of different types of coal. Unadjusted survival analysis was used to estimate the absolute risk of lung cancer, while Cox regression models compared mortality hazards for lung cancer between smoky and smokeless coal users.ResultsLung cancer mortality was substantially higher among users of smoky coal than users of smokeless coal. The absolute risks of lung cancer death before 70 years of age for men and women using smoky coal were 18% and 20%, respectively, compared with less than 0.5% among smokeless coal users of both sexes. Lung cancer alone accounted for about 40% of all deaths before age 60 among individuals using smoky coal. Compared with smokeless coal, use of smoky coal was associated with an increased risk of lung cancer death (for men, hazard ratio 36 (95% confidence interval 20 to 65); for women, 99 (37 to 266)).ConclusionsIn Xuanwei, the domestic use of smoky coal is associated with a substantial increase in the absolute lifetime risk of developing lung cancer and is likely to represent one of the strongest effects of environmental pollution reported for cancer risk. Use of less carcinogenic types of coal could translate to a substantial reduction of lung cancer risk.
| S-EPMC3431444 | biostudies-literature
Project description:In this study, the core carcinogenic elements in Xuanwei Formation coal were identified. Thirty-one samples were collected based on the age-standardized mortality rate (ASMR) of lung cancer; Si, V, Cr, Co, Ni, As, Mo, Cd, Sb, Pb, and rare earth elements and yttrium (REYs) were analyzed and compared; multivariate statistical analyses (CA, PCA, and FDA) were performed; and comprehensive identification was carried out by combining multivariate statistical analyses with toxicology and mineralogy. The final results indicated that (1) the high-concentration Si, Ni, V, Cr, Co, and Cd in coal may have some potential carcinogenic risk. (2) The concentrations of Cr, Ni, As, Mo, Cd, and Pb meet the zoning characteristics of the ASMR, while the Si concentration is not completely consistent. (3) The REY distribution pattern in Longtan Formation coal is lower than that in Xuanwei Formation coal, indicating that the materials of these elements in coal are different. (5) The heatmap divides the sampling sites into two clusters and subtypes in accordance with carcinogenic zoning based on the ASMR. (6) PC1, PC2, and PC3 explain 62.629% of the total variance, identifying Co, Ni, As, Cd, Mo, Cr, and V. (7) Fisher discriminant analysis identifies Ni, Si, Cd, As, and Co based on the discriminant function. (8) Comprehensive identification reveals that Ni is the primary carcinogenic element, followed by Co, Cd, and Si in combination with toxicology. (9) The paragenesis of Si (nanoquartz), Ni, Co, and Cd is an interesting finding. In other words, carcinogenic elements Ni, Co, Cd, and Si and their paragenetic properties should receive more attention.
| S-EPMC10761687 | biostudies-literature
Project description:Tobacco and indoor air pollution from smoky coal are major causes of lung cancer in rural Xuanwei County, China. Tuberculosis has been suggested to increase lung cancer risk, but data from prior studies are limited. We conducted an analysis of data from a retrospective cohort study of 42,422 farmers in Xuanwei. In 1992, interviewers administered a standardized questionnaire that included lifetime medical history, including tuberculosis. Subjects were followed from 1976, with deaths from lung cancer ascertained through 1996. We used proportional hazards regression to assess the association between tuberculosis and subsequent lung cancer mortality. Tuberculosis was reported by 246 subjects (0.6%), and 2,459 (5.8%) died from lung cancer during follow-up. Lung cancer mortality was substantially higher in subjects with tuberculosis than in those without (25 vs. 3.1 per 1,000 person-years). The association was especially pronounced in the first 5 years after tuberculosis diagnosis (hazard ratios [HRs] ranging 6.7-13) but remained strong 5-9.9 years (HR 3.4, 95% CI 1.3-9.1) and 10+ years (HR 3.0, 95% CI 1.3-7.3) after tuberculosis. These associations were similar among men and women and among smoky coal users (70.5% of subjects). Adjustment for demographic characteristics, lung disease and tobacco use did not affect results. In Xuanwei, China, tuberculosis is an important risk factor for lung cancer. The increased lung cancer risk, persisting years after a tuberculosis diagnosis, could reflect the effects of chronic pulmonary inflammation and scarring arising from tuberculosis.
| S-EPMC2610239 | biostudies-literature
Project description:BackgroundThe lung cancer mortality rate in Xuanwei city is among the highest in China and adenocarcinoma is the major histological type. Lung cancer has been associated with exposure to indoor smoky coal emissions that contain high levels of polycyclic aromatic hydrocarbons; however, the pathogenesis of lung cancer has not yet been fully elucidated.MethodsWe performed whole genome sequencing with lung adenocarcinoma and corresponding non-tumor tissue to explore the genomic features of Xuanwei lung cancer. We used the Molecule Annotation System to determine and plot alterations in genes and signaling pathways.ResultsA total of 3 428 060 and 3 416 989 single nucleotide variants were detected in tumor and normal genomes, respectively. After comparison of these two genomes, 977 high-confidence somatic single nucleotide variants were identified. We observed a remarkably high proportion of C·G-A·T transversions. HECTD4, RCBTB2, KLF15, and CACNA1C may be cancer-related genes. Nine copy number variations increased in chromosome 5 and one in chromosome 7. The novel junctions were detected via clustered discordant paired ends and 1955 structural variants were discovered. Among these, we found 44 novel chromosome structural variations. In addition, EGFR and CACNA1C in the mitogen-activated protein kinase signaling pathway were mutated or amplified in lung adenocarcinoma tumor tissue.ConclusionWe obtained a comprehensive view of somatic alterations of Xuanwei lung adenocarcinoma. These findings provide insight into the genomic landscape in order to further learn about the progress and development of Xuanwei lung adenocarcinoma.
| S-EPMC5334298 | biostudies-literature
Project description:Xuanwei lung cancer (XWLC) is well-known for its high incidence and mortality, especially among non-smoking female patients. However, the molecular mechanism is still unclear. Here, we performed a comprehensive transcriptomic, proteomic, and phosphoproteomic characterization of tumors and matched normal adjacent tissues from three non-smoking female XWLC patients with lung adenocarcinoma (LUAD). Integrated transcriptome and proteome analysis revealed dysregulated molecules and pathways in tumors and identified enhanced metabolic-disease coupling. Non-coding RNAs were widely involved in post-transcriptional regulatory mechanisms to coordinate the progress of LUAD, and also partially explained the molecular differences between RNA and protein expression patterns. Phosphoproteome provided evidence support for new phosphate sites, reporting the potential roles of core kinase family members and key kinase pathways involved in metabolism, immunity, as well as homeostasis. In addition, by comparing with the previous large-scale LUAD researches, we emphasized the higher degree of oxidative phosphorylation (OXPHOS) in Xuanwei LUAD, and pointed that VIPR1 deficiency aggravated immune dysfunction. Overall, our integrated multi-omics analysis provided a powerful resource for a systematic understanding of the molecular structure of XWLC and proposed therapeutic opportunities based on redox metabolism and immune cell infiltration.
2024-01-03 | GSE165298 | GEO
Project description:OBJECTIVE:To investigate the relationship between miR-501-5p expression and the clinicopathological factors in patients with lung adenocarcinoma in Xuanwei area. METHODS:Surgical specimens of lung adenocarcinoma and paired adjacent tissues from 24 patients with lung adenocarcinoma from Xuanwei area were examined for miR-501-5p expression using microRNA microarray technique and qPCR. Chi-square test was used to analyze the association of miR-501-5P expression with the clinicopathological characteristics of the patients. Multiple regression analysis was performed to analyze the association of miR-501-5p expression with the patients' gender, age, tumor stage, and preoperative CEA level. RESULTS:MicroRNA microarray analysis and qPCR validation results revealed significantly upregulated expressions of miR-501-5p in patients with lung adenocarcinoma from Xuanwei area (Plt;0.01). The microarray data showed an up-regulation of miR-501-5p by 3.17 folds in lung adenocarcinoma tissue compared with the adjacent tissue (P=0.22376, FDR=0.071395). Chi-square test indicated that miR-501-5p expression level was associated with the patients' age (f=7.168, P=0.014), TNM stage (f=36.627, P<0.01), and preoperative serum CEA level (f=30.045, Plt;0.01), but not with the patients' gender (f=3.612, P=0.071). Multiple regression analysis revealed that miR-501-5p expression was positively correlated with the patients' age, TNM stage of the tumor, and serum CEA (Plt;0.05). CONCLUSION:miR-501-5p expression is up-regulated in lung adenocarcinoma with significant associations with the patients' age, TNM stages and serum CEA level in patients from Xuanwei area, suggesting its potential role in the tumorigenesis and progression of lung adenocarcinoma in Xuanwei area.
| S-EPMC6780435 | biostudies-literature
Project description:The high incidence of lung cancer in Xuanwei County, China has been attributed to exposure to indoor smoky coal emissions that contain polycyclic aromatic hydrocarbons (PAHs). The inflammatory response induced by coal smoke components may promote lung tumor development. We studied the association between single nucleotide polymorphisms (SNPs) in genes involved in innate immunity and lung cancer risk in a population-based case-control study (122 cases and 122 controls) in Xuanwei. A total of 1,360 tag SNPs in 149 gene regions were included in the analysis. FCER2 rs7249320 was the most significant SNP (OR: 0.30; 95% CI: 0.16-0.55; P: 0.0001; false discovery rate value, 0.13) for variant carriers. The gene regions ALOX12B/ALOX15B and KLK2 were associated with increased lung cancer risk globally (false discovery rate value <0.15). In addition, there were positive interactions between KLK15 rs3745523 and smoky coal use (OR: 9.40; P-interaction = 0.07) and between FCER2 rs7249320 and KLK2 rs2739476 (OR: 10.77; P-interaction = 0.003). Our results suggest that genetic polymorphisms in innate immunity genes may play a role in the genesis of lung cancer caused by PAH-containing coal smoke. Integrin/receptor and complement pathways as well as IgE regulation are particularly noteworthy.
| S-EPMC2666781 | biostudies-literature
Project description:Over half of the world's population is exposed to household air pollution from the burning of solid fuels at home. Household air pollution from solid fuel use is a leading risk factor for global disease and remains a major public health problem, especially in low- and mid-income countries. This is a particularly serious problem in China, where many people in rural areas still use coal for household heating and cooking. This review focuses on several decades of research carried out in Xuanwei County, Yunnan Province, where household coal use is a major source of household air pollution and where studies have linked household air pollution exposure to high rates of lung cancer. We conducted a series of case-control and cohort studies in Xuanwei to characterize the lung cancer risk in this population and the factors associated with it. We found lung cancer risk to vary substantially between different coal types, with a higher risk associated with smoky (i.e., bituminous) coal use compared to smokeless (i.e., anthracite) coal use. The installation of a chimney in homes resulted in a substantial reduction in lung cancer incidence and mortality. Overall, our research underscores the need among existing coal users to improve ventilation, use the least toxic fuel, and eventually move toward the use of cleaner fuels, such as gas and electricity.
| S-EPMC4198749 | biostudies-literature
Project description:The Xuanwei area of Yunnan Province, China, is one of the regions suffering from the highest occurrence and mortality rate of lung cancer in the world. Local residents tend to use bituminous coal as domestic fuel, which causes serious indoor air pollution and is established as the main carcinogen. After the local government carried out furnace and stove reform work, lung cancer rate including incidence and mortality among residents remains high. We herein wonder if there are specific mechanisms at protein level for the development of non-small-cell lung cancer (NSCLC) in this area. We investigated the changes of protein profiling in tumour of the patients from Xuanwei area. Tandem mass tag (TMT) was employed to screen the differential proteins between carcinoma and para-carcinoma tissues. We identified a total of 422 differentially expressed proteins, among which 162 proteins were significantly up-regulated and 260 were downregulated compared to para-carcinoma tissues. Many of the differentially expressed proteins were related to extracellular matrix (ECM)-receptor interaction, focal adhesion, PI3K/AKT pathway and ferroptosis. Further experiments on the two differential proteins, thioredoxin 2 (TXN2) and haptoglobin (HP), showed that the change of their expressions could make the lung cancer cell lines more resistant to erastin or RSL-induced ferroptosis in vitro, and promote the growth of tumour in nude mice. In conclusion, this study revealed that aberrant regulation of ferroptosis may involve in the development of lung cancer in Xuanwei area.
| S-EPMC7957160 | biostudies-literature