Dose-time-response association between occupational asbestos exposure and pleural mesothelioma

Our plain-English summary of Dose-time-response association between occupational asbestos exposure and pleural mesothelioma, by A. Lacourt, E. Lévêque, E. Guichard, et al (Occupational and Environmental Medicine, 2017).

The study

• Authors: A. Lacourt, E. Lévêque, E. Guichard, A. Gilg Soit Ilg, M.P. Sylvestre, K. Leffondré
• Journal: Occupational and Environmental Medicine
• Published: 2017;74(9):691-697
• Cited by: 27 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: Early occupational exposure to asbestos has been shown to be associated with an increased risk of pleural mesothelioma (PM), which suggests that the timing of exposure might play a role in the dose-response relationship. However, none studies has evaluated the relative impact of increasing the annual intensity of occupational exposure to asbestos at each time of the whole exposure history. Yet such evaluation would allow the comparison of the risks of PM associated with different longitudinal profiles of occupational exposure to asbestos. Our objective was to estimate the time-dependent relative impact of asbestos exposure intensity over the whole occupational history and to compare the resulting estimated risks of PM associated with different profiles of exposure, using data from a large French case-control study.

Methods: This study included 1196 male cases recruited in 1987-2006 and 2369 matched controls on birth year. Occupational exposure to asbestos was assessed using a job exposure matrix and represented in logistic regression models using a flexible weighted cumulative index of exposure.

Results: Due to much stronger weights of early doses of asbestos exposure, subjects who accumulated 20 fibres/mL over their entire job history with high doses during the first years and low doses thereafter were at higher risk of PM than those who accumulated most of the doses later (OR=2.37 (95% CI 2.01 to 2.87)).

Conclusion: This study provides new insights on the dose-time-response relationship between occupational asbestos and PM and illustrates the importance of considering timing of exposure in its association with cancer risk.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

In plain English

This French case–control study asked whether the timing of occupational asbestos exposure affects pleural mesothelioma risk. It compared 1196 men diagnosed in 1987–2006 with 2369 male population controls matched on birth year. Yearly doses were estimated from job histories with a job exposure matrix; a statistical method let the data weight each year's dose. Doses received more than 40 years before diagnosis or interview, and at young ages, were associated with higher risk than later doses. Holding other years' doses constant, an extra 1 fibre/mL in the 50th year before diagnosis or interview gave an odds ratio of 1.091 (95% CI 1.073 to 1.111), against 1.026 (95% CI 1.019 to 1.031) in the second year. Doses in the last 10 years before diagnosis still had a statistically significant effect. Among hypothetical profiles each totalling 20 fibres/mL, heavy early exposure gave an odds ratio of 2.37 (95% CI 2.01 to 2.87) versus heavy late exposure. The authors concluded that exposure over 40 years before diagnosis, or at ages 15–20, had the strongest impact. The matrix had no information on fiber type.

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: Pooled case–control study, analysed with logistic regression using a flexible weighted cumulative index of exposure (WCIE), compared with the standard unweighted cumulative index (CIE)
• Who was studied: 1196 male cases with histologically confirmed pleural mesothelioma, diagnosed in five French regions (January 1987 to December 1993) or in 22 French districts (January 1998 to December 2006). They were compared with 2369 male controls drawn from two French population-based datasets and frequency matched to cases by year of birth in 5-year groups.
• Exposure: Occupational asbestos exposure over the whole job history, estimated with a job exposure matrix. The annual dose was the product of the probability, frequency and intensity of exposure, expressed in equivalent fibres/mL. Fiber type was not recorded.
• Main results:
  • Among all subjects, 1046 of 1196 cases (87.5%) and 1423 of 2369 controls (60.1%) had ever been occupationally exposed to asbestos.
  • The odds ratio for pleural mesothelioma per 1 fibre/mL increase in total cumulative dose depended on the model used. It was 1.055 (95% CI 1.044 to 1.067) with the WCIE using time before diagnosis/interview as the time axis. It was 1.030 (95% CI 1.025 to 1.037) with the WCIE using age as the time axis. It was 1.025 (95% CI 1.019 to 1.031) with the standard CIE.
  • Doses received more than 40 years before diagnosis/interview had a stronger impact than more recent doses. A 1 fibre/mL increase in the dose received in year 50 before diagnosis/interview gave an OR of 1.091 (95% CI 1.073 to 1.111). The same increase in year 2 before diagnosis/interview gave an OR of 1.026 (95% CI 1.019 to 1.031), with all other doses constant.
  • Doses received within the 10 years before diagnosis still had a statistically significant (non-null) impact on the risk of pleural mesothelioma.
  • Doses received at a young age contributed more to risk than doses received at older ages. A 1 fibre/mL increase at age 20 gave an OR of 1.064 (95% CI 1.053 to 1.079). The same increase at age 50 gave an OR of 1.019 (95% CI 1.016 to 1.024).
  • The authors compared hypothetical exposure profiles in which both subjects accumulated 20 fibres/mL. With the WCIE model, a subject with most of the dose in early career had an OR of 2.37 (95% CI 2.01 to 2.87) compared with a subject who accumulated it late. The CIE model gives an OR of 1.00 for these two profiles by definition.
  • A hypothetical subject with high early-career doses who accumulated only 10 fibres/mL in total had an OR of 1.23 (95% CI 1.19 to 1.29) compared with a subject who accumulated 20 fibres/mL late in career (WCIE model).
• The authors' conclusion: The authors concluded that increases in annual exposure intensity more than 40 years before diagnosis, or at ages 15–20 years, had the strongest impact on pleural mesothelioma risk. They also stated that their results suggest recent exposure should not be discounted in studies of pleural mesothelioma.
• Limitations the authors state:
  • The job exposure matrix may misclassify exposure because it does not account for variability within each occupational group. The authors state that this misclassification is non-differential.
  • The job exposure matrix had no information on asbestos fiber type. The authors note that chrysotile seems to have been the most commonly used type in France.
  • Pooling two sets of cases and two sets of controls may have introduced some selection bias.

Topics

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

Medical terms in this study, explained in our Lexicon: Asbestos Exposure, Pleural Mesothelioma, Occupational Exposure, Dose-response relationship, Exposure History, Occupational History, Case-Control Study.

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)
• Dose-time response association between occupational asbestos exposure and pleural mesothelioma: authors' response — A. Lacourt, E. Leveque, et al. (2018)
• Pleural mesothelioma: dose-response relation at low levels of asbestos exposure in a French population-based case-control study — Y. Iwatsubo, J.C. Pairon, et al. (1998)
• Pleural plaques and asbestosis: dose- and time-response relationships based on HRCT data — C. Paris, S. Thierry, et al. (2009)
• Response to: 'Dose-time-response association between occupational asbestos exposure and pleural mesothelioma' by Lacourt et al — P. Boffetta, E. Pira, et al. (2018)
• Low-dose exposure to asbestos and lung cancer: dose-response relations and interaction with smoking in a population-based case-referent study in Stockholm, Sweden — P. Gustavsson, F. Nyberg, et al. (2002)

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