Extended Mortality Follow-up of a Cohort of 25,460 Workers Exposed to Acrylonitrile

Our plain-English summary of Extended Mortality Follow-up of a Cohort of 25,460 Workers Exposed to Acrylonitrile, by S. Koutros, J.H. Lubin, B.I. Graubard, et al (American Journal of Epidemiology, 2019).

The study

• Authors: S. Koutros, J.H. Lubin, B.I. Graubard, A. Blair, P.A. Stewart, L.E. Beane Freeman, D.T. Silverman
• Journal: American Journal of Epidemiology
• Published: 2019;188(8):1484-1492
• Cited by: 17 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

We extended the mortality follow-up of a cohort of 25,460 workers employed at 8 acrylonitrile (AN)-producing facilities in the United States by 21 years. Using 8,124 deaths and 1,023,922 person-years of follow-up, we evaluated the relationship between occupational AN exposure and death. Standardized mortality ratios (SMRs) based on deaths through December 31, 2011, were calculated. Work histories and monitoring data were used to develop quantitative estimates of AN exposure. Hazard ratios were estimated by Cox proportional hazards regression. All-cause mortality and death from total cancer were less than expected compared with the US population. We observed an excess of death due to mesothelioma (SMR = 2.24, 95% confidence interval (CI): 1.39, 3.42); no other SMRs were elevated overall. Cox regression analyses revealed an elevated risk of lung and bronchial cancer (n = 808 deaths; for >12.1 ppm-year vs. unexposed, hazard ratio (HR) = 1.43, 95% CI: 1.13, 1.81; P for trend = 0.05), lagged 10 years, that was robust in sensitivity analyses adjusted for smoking and co-exposures including asbestos. Death resulting from bladder cancer (for >2.56 ppm vs. unexposed, lagged 10-year HR = 2.96, 95% CI: 1.38, 6.34; P for trend = 0.02) and pneumonitis (for >3.12 ppm-year vs. unexposed, HR = 4.73, 95% CI: 1.42, 15.76; P for trend = 0.007) was also associated with AN exposure. We provide additional evidence of an association between AN exposure and lung cancer, as well as possible increased risk for death due to bladder cancer and pneumonitis.

Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2019.

In plain English

This study followed 25,460 workers at eight US acrylonitrile (AN) plants for deaths through 2011, extending follow-up by 21 years. The authors compared deaths with US rates and analyzed estimated AN exposure levels. There were 8,124 deaths, fewer than expected. Mesothelioma deaths (21, counted only under ICD-10 coding) were more than twice the expected number (SMR 2.24, 95% CI 1.39 to 3.42). The excess was statistically significant only in AN-exposed workers, and mesothelioma was not significantly associated with AN level. An expert scored each job's likelihood of asbestos exposure; no asbestos measurements were available. Workers with more than 12.1 ppm-years of cumulative AN exposure (lagged 10 years) had a higher lung cancer death rate than unexposed workers (hazard ratio 1.43, 95% CI 1.13 to 1.81). This stayed raised after adjusting for the asbestos score and among workers unlikely to have had asbestos exposure. Higher AN exposure was also associated with bladder cancer and pneumonitis deaths. The authors concluded there is evidence of an association between AN and lung cancer, and a possible link with bladder cancer and pneumonitis.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Cohort mortality study (extended follow-up of an existing cohort), with comparisons to US population death rates (standardized mortality ratios) and internal Cox regression comparisons by exposure level
• Who was studied: 25,460 workers employed at least one day at any of eight US acrylonitrile-producing plants after AN operations began (1952-1965), hired 1942-1983, followed for deaths through December 31, 2011; 8,124 deaths and 1,023,922 person-years
• Exposure: Acrylonitrile, estimated from work histories, plant records and monitoring data as cumulative exposure (ppm-years), average intensity (ppm) and duration (years), with exposure data only through 1983. Asbestos co-exposure was scored by an expert as a probability of exposure for each job (0 unlikely, 1-3 low likelihood, 4-5 high likelihood); no asbestos measurements were available. Potential exposure to 340 other substances was also assessed (yes or no).
• Main results:
  • Deaths from all causes in the whole cohort were lower than expected compared with the US population: SMR 0.79 (95% CI 0.78, 0.81), based on 8,124 deaths
  • Mesothelioma (ICD-10 coded deaths only): 21 deaths, SMR 2.24 (95% CI 1.39, 3.42) overall
  • Mesothelioma by AN exposure: AN-unexposed workers SMR 1.93 (95% CI 0.63, 4.50; 5 deaths); AN-exposed workers SMR 2.36 (95% CI 1.35, 3.83; 16 deaths)
  • In internal comparisons, the authors found no significant association between AN exposure level and mesothelioma
  • Lung and bronchus cancer (808 deaths): for the highest fifth of cumulative AN exposure (more than 12.1 ppm-years, lagged 10 years) versus unexposed workers, HR 1.43 (95% CI 1.13, 1.81), p for trend 0.05. Average intensity and duration of exposure were not significantly associated.
  • Lung cancer by asbestos exposure score, compared with a score of 0: score 1-3, HR 1.01 (95% CI 0.80, 1.27); score 4-5, HR 1.32 (95% CI 1.10, 1.58)
  • Among workers with an asbestos probability score of 0, the lung cancer HR in the top fifth of cumulative AN exposure was 1.63 (95% CI 1.17, 2.26). After adjusting for asbestos exposure probability, the top-fifth HR was 1.32 (95% CI 1.03, 1.69).
  • In the smoking sub-cohort, among AN-exposed workers, the lung cancer HR for more than 12.1 ppm-years was 1.32 (95% CI 0.55, 3.17) adjusted for smoking status and 1.46 (95% CI 0.62, 3.46) adjusted for duration smoked
  • Bladder cancer: workers in the top third of average AN exposure (more than 2.56 ppm) versus unexposed workers had HR 2.96 (95% CI 1.38, 6.34), p for trend 0.02, based on 13 deaths in that group
  • Pneumonitis due to solids or liquids: for cumulative AN exposure above 3.12 ppm-years versus unexposed workers, HR 4.73 (95% CI 1.42, 15.76), p for trend 0.007
• The authors' conclusion: The authors concluded that the study provides evidence of an association between AN exposure and lung cancer death, and a possible link between AN and death from bladder cancer and pneumonitis. They interpreted the mesothelioma excess as indicating the presence of asbestos, and judged confounding of the lung cancer finding by asbestos to be minimal.
• Limitations the authors state:
  • Asbestos and other co-exposures were assessed only qualitatively
  • Work histories and exposure estimates were available only through 1983, so AN exposure is likely underestimated for workers still employed after that
  • Nondifferential misclassification of AN exposure, which tends to dilute the hazard ratios
  • Small numbers of deaths for many outcomes limited analyses of rarer outcomes
  • Many comparisons were made, which increases the chance of a chance finding
  • Smoking information was available only for a sub-cohort sample, and adjustment for smoking was not possible for bladder cancer

Topics

Medical terms in this study, explained in our Lexicon: standardized mortality ratio (SMR), Hazard Ratio, Mesothelioma, confidence interval, Pneumonitis, Lung Cancer.

Related studies

• French cohort of the uranium processing workers: mortality pattern after 30-year follow-up — I. Guseva Canu, E. Cardis, et al. (2010)
• Extended mortality follow-up among men and women in a U.S. furniture workers union — B.A. Miller, A. Blair, et al. (1994)
• Extended follow-up of lung cancer and non-malignant respiratory disease mortality among California diatomaceous earth workers — L.G. Gallagher, R.M. Park, et al. (2015)
• An updated historical cohort mortality study of workers exposed to asbestos in a refitting shipyard, 1947-2007 — K. Tomioka, Y. Natori, et al. (2011)
• Mortality and cancer morbidity in a cohort of Canadian petroleum workers — R.J. Lewis, A.R. Schnatter, et al. (2003)
• Cohort mortality study of rock salt workers in Italy — M. Tarchi, D. Orsi, et al. (1994)

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