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Original research
Alterations to biomarkers related to long-term exposure to diesel exhaust at concentrations below occupational exposure limits in the European Union and the USA
  1. Jason YY Wong1,2,
  2. Batel Blechter2,
  3. Bryan A Bassig2,
  4. Yufei Dai3,
  5. Roel Vermeulen4,
  6. Wei Hu2,
  7. Mohammad L Rahman2,
  8. Huawei Duan3,
  9. Yong Niu3,
  10. George S Downward4,
  11. Shuguang Leng5,6,
  12. Bu-Tian Ji2,
  13. Wei Fu7,
  14. Jun Xu8,
  15. Kees Meliefste4,
  16. Baosen Zhou9,
  17. Jufang Yang7,
  18. Dianzhi Ren7,
  19. Meng Ye3,
  20. Xiaowei Jia3,
  21. Tao Meng3,
  22. Ping Bin3,
  23. H. Dean Hosgood10,
  24. Nathaniel Rothman2,
  25. Debra T Silverman2,
  26. Yuxin Zheng11,
  27. Qing Lan2
  1. 1 Epidemiology and Community Health Branch, National Heart Lung and Blood Institute, Bethesda, Maryland, USA
  2. 2 Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
  3. 3 National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China
  4. 4 The Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands
  5. 5 Division of Epidemiology, Biostatistics, and Preventive Medicine, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA
  6. 6 Cancer Control and Population Sciences, University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico, USA
  7. 7 Chaoyang Center for Disease Control and Prevention, Chaoyang, Lianing, China
  8. 8 Division of Community Medicine and Public Health Practice, Hong Kong University, Hong Kong, Hong Kong, China
  9. 9 China Medical University, Liaoning, Shenyang, China
  10. 10 Division of Epidemiology, Yeshiva University Albert Einstein College of Medicine, Bronx, New York, USA
  11. 11 School of Public Health, Qingdao University, Qingdao, China
  1. Correspondence to Dr Jason YY Wong, Epidemiology and Community Health Branch, National Heart Lung and Blood Institute, Bethesda, Maryland 20892, USA; jason.wong{at}


Background We previously found that occupational exposure to diesel engine exhaust (DEE) was associated with alterations to 19 biomarkers that potentially reflect the mechanisms of carcinogenesis. Whether DEE is associated with biological alterations at concentrations under existing or recommended occupational exposure limits (OELs) is unclear.

Methods In a cross-sectional study of 54 factory workers exposed long-term to DEE and 55 unexposed controls, we reanalysed the 19 previously identified biomarkers. Multivariable linear regression was used to compare biomarker levels between DEE-exposed versus unexposed subjects and to assess elemental carbon (EC) exposure-response relationships, adjusted for age and smoking status. We analysed each biomarker at EC concentrations below the US Mine Safety and Health Administration (MSHA) OEL (<106 µg/m3), below the European Union (EU) OEL (<50 µg/m3) and below the American Conference of Governmental Industrial Hygienists (ACGIH) recommendation (<20 µg/m3).

Results Below the MSHA OEL, 17 biomarkers were altered between DEE-exposed workers and unexposed controls. Below the EU OEL, DEE-exposed workers had elevated lymphocytes (p=9E-03, false discovery rate (FDR)=0.04), CD4+ count (p=0.02, FDR=0.05), CD8+ count (p=5E-03, FDR=0.03) and miR-92a-3p (p=0.02, FDR=0.05), and nasal turbinate gene expression (first principal component: p=1E-06, FDR=2E-05), as well as decreased C-reactive protein (p=0.02, FDR=0.05), macrophage inflammatory protein-1β (p=0.04, FDR=0.09), miR-423-3p (p=0.04, FDR=0.09) and miR-122-5p (p=2E-03, FDR=0.02). Even at EC concentrations under the ACGIH recommendation, we found some evidence of exposure-response relationships for miR-423-3p (ptrend=0.01, FDR=0.19) and gene expression (ptrend=0.02, FDR=0.19).

Conclusions DEE exposure under existing or recommended OELs may be associated with biomarkers reflective of cancer-related processes, including inflammatory/immune response.

  • epidemiology
  • cross-sectional studies
  • biological monitoring
  • air pollution, indoor

Data availability statement

Data are available on reasonable request. Data are available on reasonable request at the discretion of the senior authors.

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Data availability statement

Data are available on reasonable request. Data are available on reasonable request at the discretion of the senior authors.

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  • Contributors Wrote and edited manuscript: all authors. Designed study: QL, NR, RV, DTS. Data analysis: JW, BB, WH, GSD. Data management: WH. Study supervision: DTS, YZ, QL. Exposure assessment: RV, GSD, KM, WH. DTS, YZ, QL are co-supervised authors. Guarantor: JW.

  • Funding This work is partly supported by National Natural Science Foundation of China (NSFC 91643203; NSFC 81130050) and intramural funding from the National Institutes of Health/National Cancer Institute / Division of Cancer Epidemiology and Genetics (HHSN261201500229P).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.