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Original research
Elevated Alu retroelement copy number among workers exposed to diesel engine exhaust
  1. Jason Y.Y. Wong1,
  2. Richard Cawthon2,
  3. Yufei Dai3,
  4. Roel Vermeulen4,
  5. Bryan A. Bassig1,
  6. Wei Hu1,
  7. Huawei Duan3,
  8. Yong Niu3,
  9. George S. Downward4,
  10. Shuguang Leng5,
  11. Bu-Tian Ji1,
  12. Wei Fu6,
  13. Jun Xu7,
  14. Kees Meliefste4,
  15. Baosen Zhou8,
  16. Jufang Yang6,
  17. Dianzhi Ren6,
  18. Meng Ye3,
  19. Xiaowei Jia3,
  20. Tao Meng3,
  21. Ping Bin3,
  22. H. Dean Hosgood, III9,
  23. Debra T. Silverman1,
  24. Nathaniel Rothman1,
  25. Yuxin Zheng3,
  26. Qing Lan1
  1. 1 Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA
  2. 2 Department of Human Genetics, University of Utah, Salt Lake City, Utah, USA
  3. 3 National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China
  4. 4 Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands
  5. 5 Department of Internal Medicine, School of Medicine, University of New Mexico, Albuquerque, New Mexico, USA
  6. 6 Chaoyang Center for Disease Control and Prevention, Chaoyang, Liaoning, China
  7. 7 Hong Kong University, Hong Kong, China
  8. 8 China Medical University, Shenyang, Liaoning, China
  9. 9 Division of Epidemiology, Albert Einstein College of Medicine, Yeshiva University, New York, New York, USA
  1. Correspondence to Dr Jason Y.Y. Wong, Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA; jason.wong{at}nih.gov

Abstract

Background Millions of workers worldwide are exposed to diesel engine exhaust (DEE), a known genotoxic carcinogen. Alu retroelements are repetitive DNA sequences that can multiply and compromise genomic stability. There is some evidence linking altered Alu repeats to cancer and elevated mortality risks. However, whether Alu repeats are influenced by environmental pollutants is unexplored. In an occupational setting with high DEE exposure levels, we investigated associations with Alu repeat copy number.

Methods A cross-sectional study of 54 male DEE-exposed workers from an engine testing facility and a comparison group of 55 male unexposed controls was conducted in China. Personal air samples were assessed for elemental carbon, a DEE surrogate, using NIOSH Method 5040. Quantitative PCR (qPCR) was used to measure Alu repeat copy number relative to albumin (Alb) single-gene copy number in leucocyte DNA. The unitless Alu/Alb ratio reflects the average quantity of Alu repeats per cell. Linear regression models adjusted for age and smoking status were used to estimate relations between DEE-exposed workers versus unexposed controls, DEE tertiles (6.1–39.0, 39.1–54.5 and 54.6–107.7 µg/m3) and Alu/Alb ratio.

Results DEE-exposed workers had a higher average Alu/Alb ratio than the unexposed controls (p=0.03). Further, we found a positive exposure–response relationship (p=0.02). The Alu/Alb ratio was highest among workers exposed to the top tertile of DEE versus the unexposed controls (1.12±0.08 SD vs 1.06±0.07 SD, p=0.01).

Conclusion Our findings suggest that DEE exposure may contribute to genomic instability. Further investigations of environmental pollutants, Alu copy number and carcinogenesis are warranted.

  • air pollution
  • genetic predisposition to disease
  • cross-sectional studies
  • indoor

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Footnotes

  • Contributors JW: study ideation and design, manuscript composition and statistical analysis. RC: study ideation, manuscript composition and laboratory assays. YD, HD, YN, JX, BZ, DR and DH: data collection and manuscript composition. RV: study ideation and design, data collection, exposure assessment, statistical analysis and manuscript composition. BB: data management and manuscript composition. WH: exposure assessment, data collection, data management, statistical analysis and manuscript composition. GSD: exposure assessment and manuscript composition. SL, BTJ, WF, JY, MY, XJ, TM and PB: manuscript composition. KM: exposure assessment, data collection and manuscript composition. DTS, NR, YZ and QL: study ideation and design, data collection, manuscript composition, statistical analysis and co-supervision of the study. All authors reviewed and approved the manuscript.

  • Funding This work was supported by intramural funds from the National Cancer Institute and the National Institutes of Health (Project: 1ZIACP010120-24) and the Key Program of National Natural Science Foundation of China.

  • Competing interests None declared.

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

  • Author note Bryan A. Bassig is currently employed by the US Centers for Disease Control and Prevention, National Center for Health Statistics. All work and participation in this study was conducted while employed by the US National Cancer Institute.

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