Combined effects and potential mechanisms of volatile organic compounds on thyroid disease in the US population: An integrated epidemiological and computational toxicology study

Objective: Our study aims to investigate the association between blood VOCs and thyroid diseases in US population and reveal the underlying mechanisms. Methods: NHANES 2011–2016 data were used to explore the association between blood VOC levels and thyroid disease through Weighted Quantile Sum (WQS)...

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Main Authors: Qun Lu, Zhilei Mao, Yanling Chen, Kun Zhou
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S0147651325006736
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author Qun Lu
Zhilei Mao
Yanling Chen
Kun Zhou
author_facet Qun Lu
Zhilei Mao
Yanling Chen
Kun Zhou
author_sort Qun Lu
collection DOAJ
description Objective: Our study aims to investigate the association between blood VOCs and thyroid diseases in US population and reveal the underlying mechanisms. Methods: NHANES 2011–2016 data were used to explore the association between blood VOC levels and thyroid disease through Weighted Quantile Sum (WQS) regression, logistic regression, and smooth curve fitting. Dibromochloromethane-related and thyroid disease targets were obtained from TargetNet, SuperPred, GeneCards, and GEO. A protein-protein interaction (PPI) network was constructed using STRING, and GO/KEGG enrichment analyses were performed using DAVID. Molecular docking and core target validation were carried out with Autodock Vina 1.1.2, GEPIA, and HPA databases. Results: After adjusting for covariates, higher levels of blood Dibromochloromethane and Chloroform were associated with higher risks of thyroid disease (p < 0.05). We also found nonlinear associations of Dibromochloromethane and Chloroform levels with risk of thyroid disease at lower concentrations (p < 0.05). Ten proteins were identified as core targets for the effects of Dibromochloromethane on thyroid disease, and mainly enriched the Apelin, HIF-1, and Thyroid hormone signaling pathways. External validation revealed upregulation of CTSB, PLAT, and MTOR, and downregulation of SERPINE1, NOS3, with SLC9A1 and XDH being associated with thyroid carcinoma stage. Conclusion: Positive associations between blood Dibromochloromethane and Chloroform levels and thyroid disease were observed. Dibromochloromethane interacts with core targets such as MTOR, NOS3, and SLC9A1, influencing thyroid disease progression. With the widespread exposure to VOCs worldwide, this will deepen and enrich our understanding of the potential mechanism of Dibromochloromethane in thyroid disease and provide a theoretical basis for subsequent studies.
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spelling doaj-art-74b7b4f830644bb5ac9116d7bfd8951d2025-08-20T03:53:52ZengElsevierEcotoxicology and Environmental Safety0147-65132025-06-0129811833710.1016/j.ecoenv.2025.118337Combined effects and potential mechanisms of volatile organic compounds on thyroid disease in the US population: An integrated epidemiological and computational toxicology studyQun Lu0Zhilei Mao1Yanling Chen2Kun Zhou3Department of Prenatal Diagnosis, Women's Hospital of Nanjing Medical University, Nanjing 210004, ChinaDepartment of Child Healthcare, Changzhou Maternity and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou 213003, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaKey Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, ChinaKey Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Corresponding author at: Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China.Objective: Our study aims to investigate the association between blood VOCs and thyroid diseases in US population and reveal the underlying mechanisms. Methods: NHANES 2011–2016 data were used to explore the association between blood VOC levels and thyroid disease through Weighted Quantile Sum (WQS) regression, logistic regression, and smooth curve fitting. Dibromochloromethane-related and thyroid disease targets were obtained from TargetNet, SuperPred, GeneCards, and GEO. A protein-protein interaction (PPI) network was constructed using STRING, and GO/KEGG enrichment analyses were performed using DAVID. Molecular docking and core target validation were carried out with Autodock Vina 1.1.2, GEPIA, and HPA databases. Results: After adjusting for covariates, higher levels of blood Dibromochloromethane and Chloroform were associated with higher risks of thyroid disease (p < 0.05). We also found nonlinear associations of Dibromochloromethane and Chloroform levels with risk of thyroid disease at lower concentrations (p < 0.05). Ten proteins were identified as core targets for the effects of Dibromochloromethane on thyroid disease, and mainly enriched the Apelin, HIF-1, and Thyroid hormone signaling pathways. External validation revealed upregulation of CTSB, PLAT, and MTOR, and downregulation of SERPINE1, NOS3, with SLC9A1 and XDH being associated with thyroid carcinoma stage. Conclusion: Positive associations between blood Dibromochloromethane and Chloroform levels and thyroid disease were observed. Dibromochloromethane interacts with core targets such as MTOR, NOS3, and SLC9A1, influencing thyroid disease progression. With the widespread exposure to VOCs worldwide, this will deepen and enrich our understanding of the potential mechanism of Dibromochloromethane in thyroid disease and provide a theoretical basis for subsequent studies.http://www.sciencedirect.com/science/article/pii/S0147651325006736Volatile organic compoundsThyroid diseaseWQS regressionDibromochloromethaneNHANESComputational toxicology
spellingShingle Qun Lu
Zhilei Mao
Yanling Chen
Kun Zhou
Combined effects and potential mechanisms of volatile organic compounds on thyroid disease in the US population: An integrated epidemiological and computational toxicology study
Ecotoxicology and Environmental Safety
Volatile organic compounds
Thyroid disease
WQS regression
Dibromochloromethane
NHANES
Computational toxicology
title Combined effects and potential mechanisms of volatile organic compounds on thyroid disease in the US population: An integrated epidemiological and computational toxicology study
title_full Combined effects and potential mechanisms of volatile organic compounds on thyroid disease in the US population: An integrated epidemiological and computational toxicology study
title_fullStr Combined effects and potential mechanisms of volatile organic compounds on thyroid disease in the US population: An integrated epidemiological and computational toxicology study
title_full_unstemmed Combined effects and potential mechanisms of volatile organic compounds on thyroid disease in the US population: An integrated epidemiological and computational toxicology study
title_short Combined effects and potential mechanisms of volatile organic compounds on thyroid disease in the US population: An integrated epidemiological and computational toxicology study
title_sort combined effects and potential mechanisms of volatile organic compounds on thyroid disease in the us population an integrated epidemiological and computational toxicology study
topic Volatile organic compounds
Thyroid disease
WQS regression
Dibromochloromethane
NHANES
Computational toxicology
url http://www.sciencedirect.com/science/article/pii/S0147651325006736
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