Multidimensional analysis of the effect of occupational exposure to organic solvents on lung cancer risk: the ICARE study

Our plain-English summary of Multidimensional analysis of the effect of occupational exposure to organic solvents on lung cancer risk: the ICARE study, by F. Mattei, S. Liverani, F. Guida, et al (Occupational and Environmental Medicine, 2016).

The study

• Authors: F. Mattei, S. Liverani, F. Guida, M. Matrat, S. Cenée, L. Azizi, G. Menvielle, M. Sanchez, C. Pilorget, B. Lapôtre-Ledoux, D. Luce, S. Richardson, I. Stücker, ICARE Study Group
• Journal: Occupational and Environmental Medicine
• Published: 2016;73(6):368-77
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: The association between lung cancer and occupational exposure to organic solvents is discussed. Since different solvents are often used simultaneously, it is difficult to assess the role of individual substances.

Objectives: The present study is focused on an in-depth investigation of the potential association between lung cancer risk and occupational exposure to a large group of organic solvents, taking into account the well-known risk factors for lung cancer, tobacco smoking and occupational exposure to asbestos.

Methods: We analysed data from the Investigation of occupational and environmental causes of respiratory cancers (ICARE) study, a large French population-based case-control study, set up between 2001 and 2007. A total of 2276 male cases and 2780 male controls were interviewed, and long-life occupational history was collected. In order to overcome the analytical difficulties created by multiple correlated exposures, we carried out a novel type of analysis based on Bayesian profile regression.

Results: After analysis with conventional logistic regression methods, none of the 11 solvents examined were associated with lung cancer risk. Through a profile regression approach, we did not observe any significant association between solvent exposure and lung cancer. However, we identified clusters at high risk that are related to occupations known to be at risk of developing lung cancer, such as painters.

Conclusions: Organic solvents do not appear to be substantial contributors to the occupational risk of lung cancer for the occupations known to be at risk.

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In plain English

This French case-control study (ICARE, 2001 to 2007) examined whether men's job exposure to organic solvents was linked to lung cancer. Of 2276 interviewed men with lung cancer and 2780 without, 2260 cases and 2780 controls were analysed. Exposures were estimated from job histories; analyses adjusted for age, district, smoking and asbestos. Analysed singly, white spirits were significantly linked to lung cancer only at medium exposure (odds ratio 1.66, 95% CI 1.12 to 2.46), with no dose-response pattern. The authors reported no association with all solvents in one model, though the table shows a significantly lower odds ratio for low tetrahydrofuran exposure (0.19, 95% CI 0.04 to 0.79; 3 cases, 10 controls). Bayesian clustering split the men into 13 groups. Only two, both with high asbestos exposure, had risk significantly above average. The higher-risk group also featured white spirits and low benzene; construction painters were 35% of its jobs. Simulations varying white spirits and benzene showed a small, non-significant risk shift. The authors concluded that solvents do not appear to be substantial contributors to occupational lung cancer risk in these occupations.

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: Multicentre population-based case-control study (ICARE), analysed with conventional, stepwise and ridge logistic regression and with Bayesian profile regression (clustering)
• Who was studied: Men from 10 French départements, 2001 to 2007. ICARE interviewed 2276 male lung cancer cases and 2780 male population controls. After excluding men with unknown working history and cases with no known exposure, Table 1 lists 2260 cases and 2780 controls. Individual regression models used somewhat smaller numbers. Women (650 cases, 775 controls) took part in ICARE but were not analysed because too few were exposed.
• Exposure: Lifetime occupational exposure to organic solvents (chlorinated, fuels and petroleum-based, and oxygenated), estimated with job-exposure matrices as a Cumulative Exposure Index in low, medium and high levels. Eleven solvents were analysed: trichloroethylene, benzene, white spirits, kerosene/diesel oil/fuel oils, special boiling point spirits, gasoline, alcohol, ketones/esters, diethyl ether, ethylene glycol and tetrahydrofuran. Solvents with fewer than 15 exposed men were excluded: carbon tetrachloride, chloroform, tetrachloroethylene and methylene chloride. Occupational asbestos exposure (fiber type not specified) was estimated with a separate job-exposure matrix and used as an adjustment factor and in the clustering.
• Main results:
  • Analysing one solvent at a time, white spirits were associated with lung cancer at medium exposure (OR 1.66, 95% CI 1.12 to 2.46). At high exposure the association was borderline (OR 1.36, 95% CI 0.92 to 2.02). No dose-response relationship was seen.
  • The authors wrote that the model including all solvents showed no association with lung cancer.
  • In Table 2, the model including all solvents gave a statistically significant lower odds ratio for low tetrahydrofuran exposure (OR 0.19, 95% CI 0.04 to 0.79), based on 3 cases and 10 controls. A similar result appeared when tetrahydrofuran was analysed alone (OR 0.22, 95% CI 0.05 to 0.94). The authors' text does not comment on it.
  • Stepwise selection kept two solvents. White spirits were associated with lung cancer at medium exposure (OR 1.67, 95% CI 1.13 to 2.48). Tetrahydrofuran was not significantly associated.
  • Profile regression divided the men into 13 clusters. Only clusters 11 and 13 had log odds ratios significantly higher than the average for the whole sample.
  • Cluster 13 (139 men) had the highest risk: log odds ratio 0.74, 95% credible interval 0.32 to 1.16, compared with the non-exposed cluster 5. It was characterised by high levels of asbestos and white spirits and a low level of benzene. Construction painters made up 35% of its job distribution.
  • Cluster 11 (194 men, the largest cluster) had a log odds ratio of 0.55, 95% credible interval 0.2 to 0.91, compared with cluster 5. It was characterised by high asbestos exposure and a low level of ketones/esters. Its jobs were 14% plumbers, 13% carpenters and joinery, and 4% sheet-metal workers.
  • Simulated exposure scenarios that varied white spirits and benzene levels showed only a small, non-significant shift in predicted risk, with wide credible intervals.
  • Sensitivity analyses using different probability cut-offs for solvent exposure gave similar results.
• The authors' conclusion: The authors concluded that organic solvents do not appear to be substantial contributors to the occupational lung cancer risk of occupations known to be at risk, such as painters, plumbers and pipe fitters, and carpenters and joiners. They noted that these occupations are exposed to other known or suspected lung carcinogens, including asbestos, and that which agents raise their risk remains an open question.
• Limitations the authors state:
  • Because of the large number of participants, experts could not assess exposure (the gold standard). Job-exposure matrices were used instead, with a risk of non-differential misclassification.
  • The many tests performed raise multiple comparison issues. Highly correlated exposures made the logistic regression results unstable and hard to interpret.
  • Women could not be analysed because too few were exposed.
  • No sensitivity analysis was possible for the asbestos exposure cut-off.
  • Cluster 12 was too small to give a stable risk estimate.

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, Case-Control Study, Occupational History.

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