Mesothelioma in Sweden: Dose-Response Analysis for Exposure to 29 Potential Occupational Carcinogenic Agents

Our plain-English summary of Mesothelioma in Sweden: Dose-Response Analysis for Exposure to 29 Potential Occupational Carcinogenic Agents, by N. Plato, J.I. Martinsen, K. Kjaerheim, et al (Safety and Health at Work, 2018).

The study

• Authors: N. Plato, J.I. Martinsen, K. Kjaerheim, P. Kyyronen, P. Sparen, E. Weiderpass
• Journal: Safety and Health at Work
• Published: 2018;9(3):290-295
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: There is little information on the dose-response relationship between exposure to occupational carcinogenic agents and mesothelioma. This study aimed to investigate this association as well as the existence of agents other than asbestos that might cause mesothelioma.

Methods: The Swedish component of the Nordic Occupational Cancer (NOCCA) study consists of 6.78 million individuals with detailed information on occupation. Mesothelioma diagnoses recorded in 1961-2009 were identified through linkage to the Swedish Cancer Registry. We determined cumulative exposure, time of first exposure, and maximum exposure intensity by linking data on occupation to the Swedish NOCCA job-exposure matrix, which includes 29 carcinogenic agents and corresponding exposure for 283 occupations. To assess the risk of mesothelioma, we used conditional logistic regression models to estimate hazard ratios and 95% confidence intervals.

Results: 2,757 mesothelioma cases were identified in males, including 1,416 who were exposed to asbestos. Univariate analyses showed not only a significant excess risk for maximum exposure intensity, with a hazard ratio of 4.81 at exposure levels 1.25-2.0 fb/ml but also a clear dose-response effect for cumulative exposure with a 30-, 40-, and 50-year latency time. No convincing excess risk was revealed for any of the other carcinogenic agents included in the Swedish NOCCA job-exposure matrix.

Conclusion: When considering asbestos exposure, past exposure, even for short periods, might be enough to cause mesothelioma of the pleura later in life.

In plain English

This Swedish study examined whether workplace exposure to asbestos and 28 other possible carcinogens was linked to pleural mesothelioma (cancer of the lung lining), and whether risk rose with dose. It compared 2,757 men diagnosed from 1961 to 2009 with 27,570 men matched by birth year. Exposure was estimated from occupations using a job-exposure matrix, not individual measurements. Without an exposure lag, men ever exposed to asbestos had a hazard ratio of 2.65 (95% CI 2.45 to 2.87) compared with unexposed men. Men in the lowest cumulative exposure group (below 1.78 fibre-years/ml) had 2.24 (95% CI 2.02 to 2.48). Hazard ratios rose with cumulative exposure when recent exposure was excluded (30-, 40- and 50-year lags). The highest maximum-intensity group (above 1.25 to 2.0 fibres/ml) had a hazard ratio of 4.81 (95% CI 4.06 to 5.70) compared with men assigned zero exposure. Some other agents, such as trichloroethylene and welding fumes, kept raised risks after asbestos adjustment. The authors judged these probably due to misclassification. They concluded that even low cumulative asbestos exposure entailed increased risk. They lacked smoking data.

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: Nested case-control study within the Swedish census-based Nordic Occupational Cancer (NOCCA) cohort. Each case was matched to 10 controls by birth year. Exposures were assigned with a job-exposure matrix, and hazard ratios were estimated by conditional logistic regression.
• Who was studied: Men in the Swedish part of the NOCCA cohort, which consists of people in the 1960, 1970, 1980 and 1990 Swedish censuses (6.78 million individuals). The study included 2,757 male cases of pleural mesothelioma diagnosed 1961 to 2009 and 27,570 male controls. Of the cases, 1,416 were rated as asbestos-exposed. Women were excluded because there were too few in exposed occupations.
• Exposure: Occupational exposure to asbestos (fiber type not specified) and 28 other agents listed as carcinogens. Exposure was estimated from the Swedish NOCCA job-exposure matrix (283 occupations, four calendar periods from 1945 to 1994). The study analysed cumulative exposure (in categories based on percentiles), maximum exposure intensity, and time since first exposure.
• Main results:
  • With no lag, men ever exposed to asbestos (1,416 cases, 7,896 controls) had a hazard ratio of 2.65 (95% CI 2.45 to 2.87) compared with unexposed men.
  • With no lag, men in the lowest cumulative asbestos exposure group (600 cases, 3,979 controls) had a hazard ratio of 2.24 (95% CI 2.02 to 2.48) compared with unexposed men. The authors' text describes this group as having cumulative doses of less than 1.78 f-y/ml and rounds the hazard ratio to 2.3. Table 2 labels the same cut-off as 1.78 f/ml.
  • The authors found a dose-response relationship between cumulative asbestos exposure and pleural mesothelioma using 30-, 40- and 50-year lag times.
  • With a 40-year lag, men in the highest cumulative asbestos category (18 cases, 41 controls) had a hazard ratio of 5.88 (95% CI 3.33 to 10.3).
  • For maximum asbestos exposure intensity, the highest category (above 1.25 to 2.0 fibres/ml; 201 cases, 619 controls) had a hazard ratio of 4.81 (95% CI 4.06 to 5.70) compared with men assigned zero exposure.
  • For the exposure index (probability times level), the highest category (above 0.8 to 1.8 fibres/ml; 27 cases, 32 controls) had a hazard ratio of 12.7 (95% CI 7.58 to 21.4).
  • By time since first asbestos exposure, hazard ratios rose from 1.74 at 0 to 9 years to 3.26 at 40 to 49 years, then fell to 2.86 at 50 or more years.
  • In the univariate model, 17 of the 29 agents were statistically significantly associated with mesothelioma risk.
  • After adjustment for asbestos, nine other agents had p less than 0.01. The other 18 agents showed no excess risk or trend.
  • Welding fumes, trichloroethylene, lead, aromatic hydrocarbon solvents and benzo(a)pyrene showed a positive significant trend. The authors considered this probably due to misclassification.
  • For the highest trichloroethylene category (63 cases, 262 controls), the asbestos-adjusted hazard ratio was 2.61 (95% CI 1.95 to 3.50).
  • The highest bitumen fumes category (24 cases, 18 controls) had an asbestos-adjusted hazard ratio of 8.45 (95% CI 4.47 to 15.96). The authors called this unexpected and could not exclude misclassification, since some occupations, such as insulators, were rated for both bitumen and asbestos.
• The authors' conclusion: The authors concluded that there was a significant dose-response relationship between asbestos exposure and pleural mesothelioma. This held for maximum intensity, and for cumulative exposure with 30-, 40- and 50-year lags. They also concluded that cumulative exposure, even at low levels, entailed increased risk, and that even short periods with cumulative doses below 1.78 f-y/ml can increase risk. They stated that time since first exposure did not show a sufficient dose-response relationship in the longest lag period (over 50 years).
• Limitations the authors state:
  • The authors could not control for potential confounders such as smoking. Alcohol data were also unavailable.
  • The job-exposure matrix gives average exposure for an occupation group, so there was no individual-level information on exposure or maximum intensity.
  • Occupation and exposure were known only every 10 years, from the censuses.
  • The job-exposure matrix could not separate asbestos from other exposures in industries where asbestos was handled, for example among mechanics.
  • Only 21 of 283 occupations had a relevant prevalence of asbestos exposure. Some exposed job titles were diluted within broad occupational categories.
  • The authors noted that exposure misclassification can bias hazard ratios towards the null.
  • There were too few women to analyse by gender.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Dose-response relationship, Carcinogenic, Cancer Registry, Cumulative Exposure, Hazard Ratio, confidence interval, Latency.

Related studies

• 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)
• Retrospective exposure assessment for carcinogenic agents in bitumen waterproofing industry in Finland and denmark — P. Anttila, P. Heikkilä, et al. (2009)
• Dose-time-response association between occupational asbestos exposure and pleural mesothelioma — A. Lacourt, E. Lévêque, et al. (2017)
• Occupational Exposure to Diesel Motor Exhaust and Lung Cancer: A Dose-Response Relationship Hidden by Asbestos Exposure Adjustment? The ICARE Study — M. Matrat, F. Guida, et al. (2015)
• Dose-time response association between occupational asbestos exposure and pleural mesothelioma: authors' response — A. Lacourt, E. Leveque, et al. (2018)
• Response to: 'Dose-time-response association between occupational asbestos exposure and pleural mesothelioma' by Lacourt et al — P. Boffetta, E. Pira, et al. (2018)

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