A new trajectory approach for investigating the association between an environmental or occupational exposure over lifetime and the risk of chronic disease: Application to smoking, asbestos, and lung cancer

Our plain-English summary of A new trajectory approach for investigating the association between an environmental or occupational exposure over lifetime and the risk of chronic disease: Application to smoking, asbestos, and lung cancer, by E. Lévêque, A. Lacourt, V. Philipps, et al (PloS One, 2020).

The study

• Authors: E. Lévêque, A. Lacourt, V. Philipps, D. Luce, P. Guénel, I. Stücker, C. Proust-Lima, K. Leffondré
• Journal: PloS One
• Published: 2020;15(8):e0236736
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Quantifying the association between lifetime exposures and the risk of developing a chronic disease is a recurrent challenge in epidemiology. Individual exposure trajectories are often heterogeneous and studying their associations with the risk of disease is not straightforward. We propose to use a latent class mixed model (LCMM) to identify profiles (latent classes) of exposure trajectories and estimate their association with the risk of disease. The methodology is applied to study the association between lifetime trajectories of smoking or occupational exposure to asbestos and the risk of lung cancer in males of the ICARE population-based case-control study. Asbestos exposure was assessed using a job exposure matrix. The classes of exposure trajectories were identified using two separate LCMM for smoking and asbestos, and the association between the identified classes and the risk of lung cancer was estimated in a second stage using weighted logistic regression and all subjects. A total of 2026/2610 cases/controls had complete information on both smoking and asbestos exposure, including 1938/1837 cases/controls ever smokers, and 1417/1520 cases/controls ever exposed to asbestos. The LCMM identified four latent classes of smoking trajectories which had different risks of lung cancer, all much stronger than never smokers. The most frequent class had moderate constant intensity over lifetime while the three others had either long-term, distant or recent high intensity. The latter had the strongest risk of lung cancer. We identified five classes of asbestos exposure trajectories which all had higher risk of lung cancer compared to men never occupationally exposed to asbestos, whatever the dose and the timing of exposure. The proposed approach opens new perspectives for the analyses of dose-time-response relationships between protracted exposures and the risk of developing a chronic disease, by providing a complete picture of exposure history in terms of intensity, duration, and timing of exposure.

In plain English

This French population-based case-control study (ICARE, 2001–2007) proposed a statistical method that sorts people into groups by the shape of their lifetime exposure history. The authors applied it to smoking and to occupational asbestos exposure in 2026 men with lung cancer and 2610 male controls. Asbestos exposure was estimated from job histories with a job exposure matrix; the article does not name fiber types. Exposed men with a cumulative exposure below 0.26 f/mL-years were placed in a low-exposed group, and the method found four further asbestos trajectory groups. Whatever the adjustment for smoking, every exposed group, including the low-exposed group, had a higher risk of lung cancer than men never occupationally exposed. Adjusted for a smoking index, the odds ratio was 1.5 (95% CI 1.1 to 2.1) for the group with the most recent exposure and 1.9 (95% CI 1.4 to 2.8) for the most distant. Smoking groups showed much stronger associations than asbestos groups. The authors noted that exposures were assessed retrospectively and that the job exposure matrix may misclassify exposure.

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: Population-based case-control study (ICARE) used to apply a proposed statistical method (latent class mixed model) that identifies classes of lifetime exposure trajectories, followed by weighted logistic regression
• Who was studied: Men from the ICARE study in 10 French geographical areas, 2001–2007. Lung cancer cases aged 18–75 were recruited from cancer registries, and controls were selected at random from the general population. Of 2276 male cases and 2780 male controls, 2026 cases and 2610 controls had complete information. 1969 cases and 1838 controls had ever smoked, and 1417 cases and 1520 controls had ever been occupationally exposed to asbestos.
• Exposure: Occupational asbestos exposure was estimated from lifetime job histories using a job exposure matrix. Annual levels were expressed in equivalent fibers per mL, and cumulative exposure in f/mL-years. Fiber types are not specified. Exposed men with cumulative exposure below 0.26 f/mL-years (505 cases, 722 controls) were placed beforehand in a low-exposed class. Smoking was measured in cigarettes per day each year.
• Main results:
  • Whatever the method of adjusting for smoking, all classes of asbestos-exposed men, including the low-exposed class (Class 5), had a higher risk of lung cancer than men never exposed to asbestos.
  • Adjusted for smoking trajectory class, the four more substantially exposed asbestos classes (Classes 1 to 4) all had odds ratios close to 2 compared with never-exposed men.
  • Adjusted for the Comprehensive Smoking Index, which gave the best fit, the class with the most distant asbestos exposure (Class 4) had OR 1.9 (95% CI 1.4 to 2.8) and the class with the most recent exposure (Class 2) had OR 1.5 (95% CI 1.1 to 2.1), both compared with never-exposed men.
  • Asbestos trajectory classes had weaker associations with lung cancer than smoking trajectory classes.
  • Among smoking classes, the recent high intensity class (Class 2) had the strongest risk compared with never smokers: OR 41.7 (95% CI 30.2 to 57.5).
  • The long-term very high intensity smoking class (Class 3) had the second strongest risk compared with never smokers: OR 22.7 (95% CI 16.0 to 31.7).
  • The distant very high intensity smoking class (Class 4) had OR 8.3 (95% CI 5.9 to 11.6), versus OR 10.1 (95% CI 7.5 to 13.5) for the constant moderate intensity class (Class 1), both compared with never smokers. The authors attribute this mainly to longer time since stopping smoking in Class 4.
• The authors' conclusion: The authors concluded that, whatever the adjusting method for smoking, the results showed an increased risk of lung cancer in all men ever occupationally exposed to asbestos, whatever the dose and timing of exposure. They also concluded that the method opens new perspectives for studying dose-time-response relationships.
• Limitations the authors state:
  • Annual average daily exposure intensity was an approximation for both smoking and asbestos.
  • Exposures were assessed retrospectively.
  • The job exposure matrix may produce differential exposure misclassification.
  • Further methodological studies are needed on how measurement error from the job exposure matrix affects the results of the trajectory model.
  • Very low exposed men had to be excluded from the asbestos trajectory model and grouped separately beforehand, because the model could not handle the many zero values.
  • The identified classes are not expected to represent exposure patterns in the general French population.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Occupational Exposure, Lung Cancer, Epidemiology, Case-Control Study, Asbestos Exposure, Exposure History.

Related studies

• Time-dependent effect of intensity of smoking and of occupational exposure to asbestos on the risk of lung cancer: results from the ICARE case-control study — E. Lévêque, A. Lacourt, et al. (2018)
• Occupational risk factors for chronic respiratory disease in a New Zealand population using lifetime occupational history — A. Hansell, R.E. Ghosh, et al. (2014)
• A Bayesian approach to assess interaction between known risk factors: the risk of lung cancer from exposure to asbestos and smoking — D. Wraith, K. Mengersen (2008)
• Quantifying the mediating effects of smoking and occupational exposures in the relation between education and lung cancer: the ICARE study — G. Menvielle, J.E. Franck, et al. (2016)
• The joint effect of asbestos exposure, tobacco smoking and alcohol drinking on laryngeal cancer risk: evidence from the French population-based case-control study, ICARE — G. Menvielle, A. Fayossé, et al. (2016)
• An approach to estimating the environmental burden of cancer from known and probable carcinogens: application to Ontario, Canada — S.L. Greco, E. MacIntyre, et al. (2020)

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