Evidence map›Paper›PMID 30300410›Full record

ArticlePloS one2018

Identification of gene expression predictors of occupational benzene exposure.

Courtney Schiffman, Cliona M McHale, Alan E Hubbard, Luoping Zhang, Reuben Thomas, Roel Vermeulen, Guilan Li, Min Shen, Stephen M Rappaport, Songnian Yin and 3 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 30% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.

  1. Pooled it
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  4. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 3 countries.

Courtney SchiffmanSchool of Public Health, University of California, Berkeley, California, United States of America.
Cliona M McHaleSchool of Public Health, University of California, Berkeley, California, United States of America.ORCID 0000-0002-8520-6117
Alan E HubbardSchool of Public Health, University of California, Berkeley, California, United States of America.
Luoping ZhangSchool of Public Health, University of California, Berkeley, California, United States of America.
Reuben ThomasSchool of Public Health, University of California, Berkeley, California, United States of America.
Roel VermeulenInstitute of Risk assessment Sciences, Utrecht University, Utrecht, the Netherlands.
Guilan LiInstitute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China.
Min ShenOccupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, NCI, NIH, DHHS, Bethesda, Maryland, United States of America.
Stephen M RappaportSchool of Public Health, University of California, Berkeley, California, United States of America.
Songnian YinInstitute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China.
Qing LanOccupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, NCI, NIH, DHHS, Bethesda, Maryland, United States of America.
Martyn T SmithSchool of Public Health, University of California, Berkeley, California, United States of America.
Nathaniel RothmanOccupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, NCI, NIH, DHHS, Bethesda, Maryland, United States of America.
University of California, Berkeley · USUnited States Department of Health and Human Services · USNational Institute for Occupational Health and Poison Control · CNUtrecht University · NL

Funding

Training CoreP42ES004705 · NIEHS · UNIVERSITY OF CALIFORNIA BERKELEY · PI MCHALE, CLIONA · 1987 to 2025
$74.6M
STOCHASTIC ANALYSIS OF FLOW AND TRANSPORT PHENOMENAP42ES005948 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FRY, REBECCA · 1992 to 2017
$45.4M
UNC-CH CENTER FOR ENVIRONMENTAL HEALTH &SUSCEPTIBILITYP30ES010126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Stephanie Engel · 2001 to 2026
$36.3M
Targeted Research Training CoreT42OH008429 · OH · UNIVERSITY OF CALIFORNIA BERKELEY · PI HARRIS ADAMSON, CARISA · 2005 to 2024
$30.0M
BIOMARKERS OF BENZENE EXPOSURE AND GENOTOXICITYR01ES006721 · NIEHS · UNIVERSITY OF CALIFORNIA BERKELEY · PI SMITH, MARTYN T · 1993 to 2007
$3.3M
NIEHS NIH HHS P30 ES010126NIEHS NIH HHS P42 ES004705NIEHS NIH HHS P42 ES005948NIEHS NIH HHS R01 ES006721NIOSH CDC HHS T42 OH008429
6 · The paper itself

Abstract

backgroundPreviously, 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.

objectivesIn 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.

methodsFirst, 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 0.203ppm).

resultsnCounter 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.

conclusionsUsing 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.

Indexed as

Occupational ExposureAdultArea Under CurveBenzeneBiomarkersCoenzyme A LigasesEosinophil Major Basic ProteinFemaleGene ExpressionHumansImmunity, InnateLectins, C-TypeLeukocytesMaleNF-kappa B p50 SubunitOligonucleotide Array Sequence AnalysisACSL1 protein, humanBenzeneBiomarkersCLEC5A protein, humanCoenzyme A LigasesEosinophil Major Basic ProteinLectins, C-TypeNF-kappa B p50 SubunitNFKB1 protein, humanPRG2 protein, humanProteoglycansReceptors, Cell SurfaceRNA, Messenger

Identifiers

PMID30300410
PMCPMC6177191
OpenAlexW2896311198

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.