Lung Cancer Mortality and Styrene Exposure in the Reinforced-Plastics Boatbuilding Industry: Evaluation of Healthy Worker Survivor Bias

Am J Epidemiol. 2021 Sep 1;190(9):1784-1792. doi: 10.1093/aje/kwab108.

Abstract

The evidence for styrene's being a human lung carcinogen has been inconclusive. Occupational cohorts within the reinforced-plastics industry are an ideal population in which to study this association because of their relatively high levels of exposure to styrene and lack of concomitant exposures to other known carcinogens. However, healthy worker survivor bias (HWSB), where healthier workers stay employed longer and thus have higher exposure potential, is a likely source of confounding bias for exposure-response associations, in part due to styrene's acute effects. Through December 31, 2016, we studied a cohort of 5,163 boatbuilders exposed to styrene in Washington State who were employed between 1959 and 1978; prior regression analyses had demonstrated little evidence for an exposure-response relationship between styrene exposure and lung cancer mortality. Based on estimates of necessary components of HWSB, we found evidence for a potentially large HWSB. Using g-estimation of a structural nested model to account for HWSB, we estimated that 1 year of styrene exposure at more than 30 parts per million accelerated time to lung cancer death by 2.29 years (95% confidence interval: 1.53, 2.94). Our results suggest possibly strong HWSB in our small cohort and indicate that large, influential studies of styrene-exposed workers may suffer from similar biases, warranting a reassessment of the evidence of long-term health effects of styrene exposure.

Keywords: g-estimation; healthy worker survivor bias; lung cancer; occupational exposure; styrene.

MeSH terms

  • Aged
  • Bias
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Lung Neoplasms / chemically induced*
  • Lung Neoplasms / mortality
  • Male
  • Manufacturing Industry* / statistics & numerical data
  • Middle Aged
  • Models, Statistical
  • Occupational Exposure / adverse effects*
  • Plastics / toxicity*
  • Regression Analysis
  • Ships*
  • Styrene / toxicity*
  • Survivors / statistics & numerical data
  • Washington / epidemiology

Substances

  • Plastics
  • Styrene