Estimating impacts of reducing acrylonitrile exposure on lung cancer mortality with the parametric g-formula

Published

May 20, 2024

Author(s)

Alexander Keil, Gregory Haber, Barry Graubard, Patricia Stewart, Debra Silverman, Stella Koutros

Abstract

Objectives: To inform the potential human carcinogenicity of acrylonitrile, we estimate associations between acrylonitrile exposures and lung cancer mortality in US workers with the objectives of 1) assessing potential for healthy worker survivor bias 2) adjusting for healthy worker survivor bias using methods from the field of causal inference and 3) assess the expected lung cancer mortality under different hypothetical occupational limits on acrylonitrile exposure. Methods: We utilized data from the Acrylonitrile Cohort Study (ACS) which comprises 25,460 workers at facilities using acrylonitrile in production in the US. Using the parametric g-formula, we estimated cumulative excess lung cancer mortality at hypothetical annualized occupational limits on acrylonitrile exposure. We compared this to expected mortality at no exposure or at observed exposure levels. This approach can adjust for healthy worker survivor bias. Results: Employment characteristics were associated with lung cancer, and exposure was also associated with leaving employment, indicating potential for healthy worker survivor bias. Relative to no hypothetical intervention, reducing historical exposure limits to 2.0, 1.0 and 0.45 ppm would have been expected to reduce lung cancer mortality by age 90 by 4.46, 95% confidence intervals (CI) = 0.78, 8.15), 5.03 (95% CI = 0.96, 9.11), and 6.45 (95% CI = 2.35, 10.58) deaths per 1,000 workers. Conclusions: Healthy worker survivor bias is a likely threat to validity in occupational studies of acrylonitrile. Our results corroborate previous findings from the ACS which found an excess hazard of lung cancer among the highest exposed workers.

Citation

Journal of Occupational and Environmental Medicine

Pub Type

Journals

Download Paper

https://doi.org/10.1136/oemed-2024-109532

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Keywords

Acrylonitrile, Lung Neoplasms, Epidemiologic Biases, Employee Health

Citation

Keil, A. , Haber, G. , Graubard, B. , Stewart, P. , Silverman, D. and Koutros, S. (2024), Estimating impacts of reducing acrylonitrile exposure on lung cancer mortality with the parametric g-formula, Journal of Occupational and Environmental Medicine, [online], https://doi.org/10.1136/oemed-2024-109532, https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=957540 (Accessed October 14, 2025)