Dataset Information

Association between occupational exposure to trichloroethylene and serum levels of microRNAs: a cross-sectional molecular epidemiology study in China.

ABSTRACT: OBJECTIVES:The objective of our study was to evaluate the association between occupational exposure to trichloroethylene (TCE), a suspected lymphomagen, and serum levels of miRNAs in a cross-sectional molecular epidemiology study of TCE-exposed workers and comparable unexposed controls in China. METHODS:Serum levels of 40 miRNAs were compared in 74 workers exposed to TCE (median: 12 ppm) and 90 unexposed control workers. Linear regression models were used to test for differences in serum miRNA levels between exposed and unexposed workers and to evaluate exposure-response relationships across TCE exposure categories using a three-level ordinal variable [i.e., unexposed,?

SUBMITTER: Lee KM

PROVIDER: S-EPMC6953905 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Association between occupational exposure to trichloroethylene and serum levels of microRNAs: a cross-sectional molecular epidemiology study in China.

Lee Kyoung-Mu KM Bassig Bryan A BA Zhang Luoping L Vermeulen Roel C RC Hu Wei W Wong Jason Y Y JYY Qiu Chuangyi C Wen Cuiju C Huang Yongshun Y Purdue Mark P MP Ji Bu-Tian BT Li Laiyu L Tang Xiaojiang X Rothman Nathaniel N Smith Martyn T MT Lan Qing Q

International archives of occupational and environmental health 20190603 8

<h4>Objectives</h4>The objective of our study was to evaluate the association between occupational exposure to trichloroethylene (TCE), a suspected lymphomagen, and serum levels of miRNAs in a cross-sectional molecular epidemiology study of TCE-exposed workers and comparable unexposed controls in China.<h4>Methods</h4>Serum levels of 40 miRNAs were compared in 74 workers exposed to TCE (median: 12 ppm) and 90 unexposed control workers. Linear regression models were used to test for differences i ...[more]

PMID: 31161417

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Project description:BackgroundOccupational exposure to trichloroethylene (TCE) has been linked to adverse health outcomes including non-Hodgkin's lymphoma and kidney and liver cancer; however, TCE's mode of action for development of these diseases in humans is not well understood.MethodsNon-targeted metabolomics analysis of plasma obtained from 80 TCE-exposed workers [full shift exposure range of 0.4 to 230 parts-per-million of air (ppma)] and 95 matched controls were completed by ultra-high resolution mass spectrometry. Biological response to TCE exposure was determined using a metabolome-wide association study (MWAS) framework, with metabolic changes and plasma TCE metabolites evaluated by dose-response and pathway enrichment. Biological perturbations were then linked to immunological, renal and exposure molecular markers measured in the same population.ResultsMetabolic features associated with TCE exposure included known TCE metabolites, unidentifiable chlorinated compounds and endogenous metabolites. Exposure resulted in a systemic response in endogenous metabolism, including disruption in purine catabolism and decreases in sulphur amino acid and bile acid biosynthesis pathways. Metabolite associations with TCE exposure included uric acid (β = 0.13, P-value = 3.6 × 10-5), glutamine (β = 0.08, P-value = 0.0013), cystine (β = 0.75, P-value = 0.0022), methylthioadenosine (β = -1.6, P-value = 0.0043), taurine (β = -2.4, P-value = 0.0011) and chenodeoxycholic acid (β = -1.3, P-value = 0.0039), which are consistent with known toxic effects of TCE, including immunosuppression, hepatotoxicity and nephrotoxicity. Correlation with additional exposure markers and physiological endpoints supported known disease associations.ConclusionsHigh-resolution metabolomics correlates measured occupational exposure to internal dose and metabolic response, providing insight into molecular mechanisms of exposure-related disease aetiology.

Project description:ObjectivesOccupational dust exposure may induce various lung diseases, including pneumoconiosis and chronic obstructive pulmonary disease (COPD). The features of combined COPD and pneumoconiosis have not been well described, and this may hamper the management. This study aimed to describe the prevalence and characteristics as well as the risk factors of the combined diseases.DesignA cross-sectional study.Setting and participants758 patients with pneumoconiosis were recruited at a single-medical centre. Of these, 675 patients with pneumoconiosis, including asbestosis, silicosis, coal workers' pneumoconiosis and other pneumoconiosis, was eligible for analysis.Primary outcome measuresCOPD was diagnosed based on clinical features and/or history of exposure to risk factors and post bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7. Clinical data were collected from predesigned medical reports. The patients underwent both chest radiograph and high-resolution CT scans. Risk factors for combined COPD and pneumoconiosis were analysed using regression analysis.ResultsCOPD prevalence overall was 32.7% (221/675) and was the highest in silicosis (84/221) and coal workers' pneumoconiosis (100/221). COPD prevalence increased with smoking pack-years, dust exposure duration and pneumoconiosis stage. Patients with combined diseases had lower body mass index, higher smoking index and worse pulmonary function. Risk factors for combined diseases included heavy smoking, silica or coal exposure and advanced pneumoconiosis. The interaction between dust exposure and smoking in COPD was also identified. The risk of combined COPD significantly increased with heavy smoking and silica or coal exposure (OR 5.49, 95% CI 3.04 to 9.93, p<0.001).ConclusionsCOPD is highly prevalent in patients with pneumoconiosis, especially patients with silicosis and coal workers' pneumoconiosis. Occupational dust exposure as well as heavy smoking is associated with an increased risk of combined COPD and pneumoconiosis, which demands an effective preventive intervention.

Project description:Trichloroethylene (TCE) is a suspected renal carcinogen. TCE-associated renal genotoxicity occurs predominantly through glutathione S-transferase (GST) conjugation and bioactivation by renal cysteine beta-lyase (CCBL1). We conducted a case-control study in Central Europe (1,097 cases and 1,476 controls) specifically designed to assess risk associated with occupational exposure to TCE through analysis of detailed job histories. All jobs were coded for organic/chlorinated solvent and TCE exposure (ever/never) as well as the frequency and intensity of exposure based on detailed occupational questionnaires, specialized questionnaires, and expert assessments. Increased risk was observed among subjects ever TCE exposed [odds ratio (OR) = 1.63; 95% confidence interval (95% CI), 1.04-2.54]. Exposure-response trends were observed among subjects above and below the median exposure [average intensity (OR = 1.38; 95% CI, 0.81-2.35; OR = 2.34; 95% CI, 1.05-5.21; P(trend) = 0.02)]. A significant association was found among TCE-exposed subjects with at least one intact GSTT1 allele (active genotype; OR = 1.88; 95% CI, 1.06-3.33) but not among subjects with two deleted alleles (null genotype; OR = 0.93; 95% CI, 0.35-2.44; P(interaction) = 0.18). Similar associations for all exposure metrics including average intensity were observed among GSTT1-active subjects (OR = 1.56; 95% CI, 0.79-3.10; OR = 2.77; 95% CI, 1.01-7.58; P(trend) = 0.02) but not among GSTT1 nulls (OR = 0.81; 95% CI, 0.24-2.72; OR = 1.16; 95% CI, 0.27-5.04; P(trend) = 1.00; P(interaction) = 0.34). Further evidence of heterogeneity was seen among TCE-exposed subjects with >or=1 minor allele of several CCBL1-tagging single nucleotide polymorphisms: rs2293968, rs2280841, rs2259043, and rs941960. These findings provide the strongest evidence to date that TCE exposure is associated with increased renal cancer risk, particularly among individuals carrying polymorphisms in genes that are important in the reductive metabolism of this chemical, and provides biological plausibility of the association in humans.

Dataset Information

Association between occupational exposure to trichloroethylene and serum levels of microRNAs: a cross-sectional molecular epidemiology study in China.

Publications

Association between occupational exposure to trichloroethylene and serum levels of microRNAs: a cross-sectional molecular epidemiology study in China.

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