Identification of Gene Expression Predictors of Occupational Benzene Exposure

Details

• Personal Author:
  Hubbard AE ; Lan Q ; Li G ; McHale CM ; Rappaport SM ; Rothman N ; Schiffman C ; Shen M ; Smith MT ; Thomas R ; Vermeulen R ; Yin S ; Zhang L
• Description:
  Background: Previously, using microarrays and mRNA-Sequencing (mRNA-Seq) we found that occupational exposure to a range of benzene levels perturbed gene expression in peripheral blood mononuclear cells. Objectives: In the current study, we sought to identify gene expression biomarkers predictive of benzene exposure below 1 part per million (ppm), the occupational standard in the U.S. Methods: First, we used the nCounter platform to validate altered expression of 30 genes in 33 unexposed controls and 57 subjects exposed to benzene (<1 to >/= 5 ppm). Second, we used SuperLearner (SL) to identify a minimal number of genes for which altered expression could predict <1 ppm benzene exposure, in 44 subjects with a mean air benzene level of 0.55 +/- 0.248 ppm (minimum 0.203 ppm). Results: nCounter and microarray expression levels were highly correlated (coefficients >0.7, p<0.05) for 26 microarray-selected genes. nCounter and mRNA-Seq levels were poorly correlated for 4 mRNA-Seq-selected genes. Using negative binomial regression with adjustment for covariates and multiple testing, we confirmed differential expression of 23 microarray-selected genes in the entire benzene-exposed group, and 27 genes in the <1 ppm-exposed subgroup, compared with the control group. Using SL, we identified 3 pairs of genes that could predict <1 ppm benzene exposure with cross-validated AUC estimates >0.9 (p<0.0001) and were not predictive of other exposures (nickel, arsenic, smoking, stress). The predictive gene pairs are PRG2/CLEC5A, NFKBI/CLEC5A, and ACSL1/ CLEC5A. They play roles in innate immunity and inflammatory responses. Conclusions: Using nCounter and SL, we validated the altered expression of multiple mRNAs by benzene and identified gene pairs predictive of exposure to benzene at levels below the US occupational standard of 1ppm. [Description provided by NIOSH]
• Subjects:
  Benzene Biomarkers Environmental Exposure Genetics Immune System Occupational Exposure Occupational Health Safety
• Keywords:
  Analytical Instruments Chemical Indicators Exposure Assessment Exposure Levels Gene Expression Genes Immune Reaction Immune System Occupational Exposure Ribonucleic Acids RNA

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• ISSN:
  1932-6203
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  California ; Maryland ; OSHA Region 3 ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  13
• Issue:
  10
• NIOSHTIC Number:
  nn:20055253
• Citation:
  PLoS One 2018 Oct; 13(10):e0205427
• Contact Point Address:
  Cliona M. McHale, School of Public Health, University of California, Berkeley, California, United States of America
• Email:
  cmchale@berkeley.edu
• CAS Registry Number:
  Benzene (CAS RN 71-43-2)
• Federal Fiscal Year:
  2019
• Performing Organization:
  University of California, Berkeley
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  PLoS One
• End Date:
  20250630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:57fcbd35305df5f2c1e1d873489bf472f5c0ccaf8923fe1b8336fe05b3fbdb51772e4310f608f7cdb241e173af2a326d628fccc41a216e406f5ccc9baab836e8
• Download URL:
  https://stacks.cdc.gov/view/cdc/217597/cdc_217597_DS1.pdf
• File Type:
  [PDF - 1.51 MB ]