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Ethylene oxide and risk of lympho-hematopoietic cancer and breast cancer: a systematic literature review and meta-analysis

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Abstract

Purpose

To conduct a systematic literature review and meta-analysis of studies of lympho-hematopoietic cancers (LHC) and breast cancer risk among persons occupationally exposed to ethylene oxide (EO).

Methods

We performed a literature search for articles available in PubMed and Web of Science databases to identify literature and subsequently systematically searched the reference lists of identified studies, published review papers and meta-analyses, as well as relevant government or regulatory documents. We qualitatively reviewed 30 studies and conducted meta-analyses on 13 studies. Pooled risk estimates were calculated using random effects models, stratifying by occupational group, cancer type and decade of publication.

Results

The overall meta-relative risks (meta-RRs) for LHC and breast cancer, respectively, were 1.48 (95% CI 1.07–2.05) and 0.97 (95% CI 0.80–1.18). The meta-RR’s for LHC among EO production and EO sterilization workers were 1.46 (95% CI 0.85–2.50) and 1.07 (95% CI 0.87–1.30), respectively. We observed higher risks of LHC in the earlier published studies, compared to the later studies, and the meta-RR’s for the 1980s, 1990s, 2000s, and the 2010s, respectively, were 3.87 (95% CI 1.87–8.01), 1.38 (95% CI 0.85–2.25), 1.05 (95% CI 0.84–1.31), and 1.19 (95% CI 0.80–1.77).

Conclusions

The most informative epidemiology studies, which were published in the 2000s and 2010s, do not support the conclusion that exposure to EO is associated with an increased risk of LHC or breast cancer.

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Notes

  1. For the purposes of consistency, values that were reported in mg/m3 were converted to ppm, assuming that 1 ppm = 1.8 mg/m3.

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Acknowledgements

The authors thank Dr. Jane Teta for providing data from the unpublished Divine (1990) study and for her helpful comments on the draft manuscript.

Funding

Earlier work on this commentary was performed under a consulting agreement between GM and the American Chemistry Council (ACC). Later work including the meta- analysis and preparation of this manuscript was performed under a consulting agreement between Cardno ChemRisk and the ACC.

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Authors and Affiliations

  1. Cardno ChemRisk, 20 Stanwix Street, Suite 505, Pittsburgh, PA, 15222, USA

    Gary M. Marsh & Stacey M. Benson

  2. Cardno ChemRisk, 30 N. LaSalle St., Suite 3910, Chicago, IL, 60602, USA

    Kara A. Keeton & Alexander S. Riordan

  3. Cardno ChemRisk, 4940 Pearl East Circle, Suite 100, Boulder, CO, 80301, USA

    Elizabeth A. Best

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  1. Gary M. Marsh
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Contributions

GMM developed the idea for the manuscript, assisted with the biostatistical approach to the analysis, and was responsible for the overall quality of work. KAK reviewed the literature and confirmed the inclusion and exclusion of various studies, drafted text, created figures, and assisted with conducting the analyses. ASR reviewed the literature and confirmed the inclusion and exclusion of various studies, drafted text, and assisted with conducting the analyses. EAB reviewed the literature and confirmed the inclusion and exclusion of various studies, drafted text, assisted with conducting the analyses, and created figures. SMB reviewed the literature and confirmed the inclusion and exclusion of various studies, drafted text, and created figures.

Corresponding author

Correspondence to Kara A. Keeton.

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Conflict of interest

The financial sponsor ACC was given the opportunity to review and comment on the draft manuscript, but the study design, the synthesis of findings, the conclusions drawn and the preparation of the manuscript are the exclusive professional work product of the authors, and may not necessarily be those of Cardno ChemRisk or ACC. GM performed part of this work as a private consultant and part as Consulting Senior Science Advisor for Epidemiology at Cardno ChemRisk. In addition to his role as a consultant, GM is Professor of Biostatistics and Director and Founder of the Center for Occupational Biostatistics and Epidemiology at the University of Pittsburgh, Graduate School of Public Health. For more than 42 years, GM has directed or co-directed epidemiological research on the potential carcinogenicity of numerous chemical agents. SB, KK, EB and AR are epidemiologists at Cardno ChemRisk with experience in environmental and occupational health research.

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Marsh, G.M., Keeton, K.A., Riordan, A.S. et al. Ethylene oxide and risk of lympho-hematopoietic cancer and breast cancer: a systematic literature review and meta-analysis. Int Arch Occup Environ Health 92, 919–939 (2019). https://doi.org/10.1007/s00420-019-01438-z

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