Pleural mesothelioma: dose-response relation at low levels of asbestos exposure in a French population-based case-control study

Our plain-English summary of Pleural mesothelioma: dose-response relation at low levels of asbestos exposure in a French population-based case-control study, by Y. Iwatsubo, J.C. Pairon, C. Boutin, et al (American Journal of Epidemiology, 1998).

The study

• Authors: Y. Iwatsubo, J.C. Pairon, C. Boutin, O. Ménard, N. Massin, D. Caillaud, E. Orlowski, F. Galateau-Salle, J. Bignon, P. Brochard
• Journal: American Journal of Epidemiology
• Published: 1998;148(2):133-42
• Cited by: 103 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

A hospital-based case-control study of the association between past occupational exposure to asbestos and pleural mesothelioma was carried out in five regions of France. Between 1987 and 1993, 405 cases and 387 controls were interviewed. The job histories of these subjects were evaluated by a group of experts for exposure to asbestos fibers according to probability, intensity, and frequency. A cumulative exposure index was calculated as the product of these three parameters and the duration of the exposed job, summed over the entire working life. Among men, the odds ratio increased with the probability of exposure and was 1.2 (95% confidence interval (CI) 0.8-1.9) for possible exposure and 3.6 (95% CI 2.4-5.3) for definite exposure. A dose-response relation was observed with the cumulative exposure index: The odds ratio increased from 1.2 (95% CI 0.8-1.8) for the lowest exposure category to 8.7 (95% CI 4.1-18.5) for the highest. Among women, the odds ratio for possible or definite exposure was 18.8 (95% CI 4.1-86.2). We found a clear dose-response relation between cumulative asbestos exposure and pleural mesothelioma in a population-based case-control study with retrospective assessment of exposure. A significant excess of mesothelioma was observed for levels of cumulative exposure that were probably far below the limits adopted in most industrial countries during the 1980s.

In plain English

This hospital-based French case-control study interviewed 405 pleural mesothelioma patients and 387 hospital controls in five regions, 1987-1993. Industrial hygiene experts rated each job for the probability, intensity and frequency of asbestos exposure. These ratings, multiplied by job duration and summed over the working life, formed a cumulative exposure index; exposure in the 20 years before diagnosis was left out. With no air measurements, its "f/ml-years" units are expert-based estimates. Among men, the odds ratio was 1.2 (95% CI 0.8-1.9, not significant) for possible and 3.6 (95% CI 2.4-5.3) for definite exposure. By cumulative exposure, it rose from 1.2 (95% CI 0.8-1.8) at 0.001-0.49 "f/ml-years" to 8.7 (95% CI 4.1-18.5) at 10 or more. For men, continuous exposure gave an odds ratio of 5.7 (95% CI 3.4-9.7) and intermittent exposure 1.8 (95% CI 1.3-2.6). Among women, possible or definite exposure gave 18.8 (95% CI 4.1-86.2), based on few exposed women. The authors concluded there was a clear dose-response relation, with excess mesothelioma at levels probably far below 1980s limits in many industrial countries. Fiber types could not be studied.

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: Hospital-based case-control study, which the authors also call population-based. Exposure was assessed retrospectively by experts.
• Who was studied: 405 patients with histologically confirmed pleural malignant mesothelioma who were alive at interview, and 387 hospital controls. Controls were matched for sex, age, place of residence and racial or ethnic origin, and came from internal medicine, ophthalmology and surgery departments. Subjects came from five French regions (Paris metropolitan area, Provence-Alpes-Cote-d'Azur, Corsica, Lorraine, Auvergne) and were interviewed between 1987 and 1993. 82 percent of cases and 81 percent of controls were men.
• Exposure: Past occupational asbestos exposure. Five industrial hygiene experts rated each job period by probability (not exposed, possible, definite), frequency (sporadic, irregular, continuous) and intensity (low, under 1 fiber/ml, up to very high, over 10 fibers/ml). The cumulative exposure index was the lifetime sum, over job periods, of probability times frequency times intensity times duration. It was expressed in "f/ml-years" in quotation marks because it was not based on measurements. Exposure in the 20 years before diagnosis was not analyzed. Fiber types were not distinguished.
• Main results:
  • Men: odds ratio 1.2 (95% CI 0.8-1.9) for possible exposure and 3.6 (95% CI 2.4-5.3) for definite exposure.
  • Men: by cumulative exposure index, the odds ratio rose from 1.2 (95% CI 0.8-1.8) in the lowest exposed category (0.001-0.49 "f/ml-years" in Table 5) to 8.7 (95% CI 4.1-18.5) in the highest (10 or more "f/ml-years" in Table 5).
  • Exposure during the 20 years before diagnosis was not included in the analysis.
  • 23 percent of cases and 35 percent of controls had cumulative exposure below 0.5 "f/ml-years".
  • Men: odds ratio 5.4 for at least 20 years in exposed jobs.
  • Men with only sporadic exposure were not at greater risk than controls.
  • Men: odds ratio 1.8 (95% CI 1.3-2.6) for intermittent exposure and 5.7 (95% CI 3.4-9.7) for continuous exposure.
  • Within cumulative exposure categories, odds ratios for continuous exposure were almost twice those for intermittent exposure, except in the 0.5-1 "f/ml-years" category.
  • The odds ratio did not increase with time since first exposure, and there was no consistent trend with age at first exposure.
  • Women: odds ratio 18.8 (95% CI 4.1-86.2) for possible and definite exposure considered together.
  • In a supplementary analysis that treated all possible-exposure jobs as unexposed, the odds ratio in the highest cumulative category was 7.8 (95% CI 3.8-16.2).
• The authors' conclusion: The authors concluded that there was a clear dose-response relation between cumulative asbestos exposure and pleural mesothelioma. They also concluded that a significant excess of mesothelioma occurred at cumulative exposures probably far below the limits adopted in many industrial countries during the 1980s.
• Limitations the authors state:
  • Patients with a known asbestos history may be more likely to be diagnosed with mesothelioma. The authors say this could have heightened the dose-response relation.
  • Using hospital controls could have caused bias. Controls included fewer blue-collar workers, and adjusting for socioeconomic category could have led to overadjustment.
  • No objective measurements were available to check the experts' evaluation, so the exposure units are not measured doses.
  • The experts thought their assessment of periods 20 or more years ago might be less accurate. This could cause misclassification and possible underestimation of the odds ratios.
  • Interviewers knew who was a case and might have interviewed cases more thoroughly.
  • The dose-response pattern is more doubtful at low doses, where exposure estimates are least certain.
  • Subjects with intermittent exposure may be misclassified more often.
  • Risk by fiber type could not be examined.
  • Few women were exposed (25 cases and two controls), so dose-response among women was not analyzed.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Dose-response relationship, Asbestos Exposure, Case-Control Study, Occupational Exposure, Cumulative Exposure, Odds Ratio, confidence interval.

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