Exposure-Response Analyses of Asbestos and Lung Cancer Subtypes in a Pooled Analysis of Case-Control Studies

Our plain-English summary of Exposure-Response Analyses of Asbestos and Lung Cancer Subtypes in a Pooled Analysis of Case-Control Studies, by A.C. Olsson, R. Vermeulen, J. Schüz, et al (Epidemiology, 2017).

The study

• Authors: A.C. Olsson, R. Vermeulen, J. Schüz, H. Kromhout, B. Pesch, S. Peters, T. Behrens, L. Portengen, D. Mirabelli, P. Gustavsson, B. Kendzia, J. Almansa, V. Luzon, J. Vlaanderen, I. Stücker, F. Guida, D. Consonni, N. Caporaso, M.T. Landi, J. Field, I. Brüske, H.E. Wichmann, J. Siemiatycki, M.E. Parent, L. Richiardi, F. Merletti, K.H. Jöckel, W. Ahrens, H. Pohlabeln, N. Plato, A. Tardón, D. Zaridze, J. McLaughlin, P. Demers, N. Szeszenia-Dabrowska, J. Lissowska, P. Rudnai, E. Fabianova, R. Stanescu Dumitru, V. Bencko, L. Foretova, V. Janout, P. Boffetta, B. Bueno-de-Mesquita, F. Forastiere, T. Brüning, K. Straif
• Journal: Epidemiology
• Published: 2017;28(2):288-299
• Cited by: 70 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Evidence is limited regarding risk and the shape of the exposure-response curve at low asbestos exposure levels. We estimated the exposure-response for occupational asbestos exposure and assessed the joint effect of asbestos exposure and smoking by sex and lung cancer subtype in general population studies.

Methods: We pooled 14 case-control studies conducted in 1985-2010 in Europe and Canada, including 17,705 lung cancer cases and 21,813 controls with detailed information on tobacco habits and lifetime occupations. We developed a quantitative job-exposure-matrix to estimate job-, time period-, and region-specific exposure levels. Fiber-years (ff/ml-years) were calculated for each subject by linking the matrix with individual occupational histories. We fit unconditional logistic regression models to estimate odds ratios (ORs), 95% confidence intervals (CIs), and trends.

Results: The fully adjusted OR for ever-exposure to asbestos was 1.24 (95% CI, 1.18, 1.31) in men and 1.12 (95% CI, 0.95, 1.31) in women. In men, increasing lung cancer risk was observed with increasing exposure in all smoking categories and for all three major lung cancer subtypes. In women, lung cancer risk for all subtypes was increased in current smokers (ORs ~two-fold). The joint effect of asbestos exposure and smoking did not deviate from multiplicativity among men, and was more than additive among women.

Conclusions: Our results in men showed an excess risk of lung cancer and its subtypes at low cumulative exposure levels, with a steeper exposure-response slope in this exposure range than at higher, previously studied levels. (See video abstract at, http://links.lww.com/EDE/B161.).

In plain English

This study pooled 14 lung cancer case–control studies from Europe and Canada (1985–2010) and analyzed 16,901 cases and 20,965 controls. The authors estimated each person's cumulative workplace asbestos exposure in fiber-years (ff/ml-years) using a job-exposure matrix built from workplace measurements, and adjusted for smoking. Among men, ever-exposure to asbestos was associated with lung cancer (odds ratio 1.24, 95% CI 1.18 to 1.31). Among women the odds ratio was 1.12 (0.95 to 1.31), so there was no statistically clear overall association. In men, risk was raised in all but the lowest exposure group (below 0.5 ff/ml-years). It was also raised among never-, former and current smokers and, the authors reported, for all three major subtypes. Among women who were current smokers, odds ratios were about two-fold at exposure above 1.2 ff/ml-years. In men, the combined effect of asbestos and smoking was more than additive. The authors concluded that in men there was excess risk at low cumulative exposure, with a steeper exposure–response slope than at higher, previously studied levels. Fiber type could not be distinguished.

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 analysis of 14 case–control studies (the SYNERGY project)
• Who was studied: Lung cancer cases and controls from 14 case–control studies in Europe and Canada, with data collected 1985–2010. After excluding people with incomplete covariate data, 16,901 lung cancer cases and 20,965 controls were analyzed.
• Exposure: Occupational asbestos exposure, estimated by linking lifetime job histories to a quantitative job-exposure matrix (SYN-JEM) built from workplace fiber measurements, and expressed as cumulative fiber-years (ff/ml-years). The authors assumed most measurements (67%) represented chrysotile, but fiber type could not be distinguished.
• Main results:
  • The fully adjusted odds ratio for ever-exposure to asbestos was 1.24 (95% CI 1.18, 1.31) in men and 1.12 (95% CI 0.95, 1.31) in women.
  • In men, only the lowest quartile of cumulative exposure (under 0.5 ff/ml-years) showed no increased risk (OR 1.06; 95% CI 0.96, 1.16).
  • In men, the highest quartile of cumulative exposure (above 2.8 ff/ml-years) had an OR of 1.38 (95% CI 1.27, 1.50).
  • In women, who had smaller numbers of exposed subjects and a lower median exposure level, there were no statistically clear increases in ORs across the overall exposure indices. The authors wrote that no increased ORs were observed.
  • Among exposed controls, women had lower cumulative exposure levels than men (median 0.57 vs 1.21 ff/ml-years).
  • In men, asbestos exposure was associated with increased lung cancer risk among never-smokers, former smokers and current smokers.
  • Among male never-smokers with exposure above the median (above 1.2 ff/ml-years), the OR for small-cell carcinoma was 2.73 (95% CI 1.39, 5.35).
  • Among female current smokers, ORs of about two-fold were seen at cumulative exposure above 1.2 ff/ml-years (all lung cancer OR 2.05, 95% CI 1.24, 3.40). Below 1.2 ff/ml-years, the all lung cancer OR was 1.22 (95% CI 0.90, 1.66).
  • Among female never-smokers, there was an association with small-cell lung cancer even at exposure below 1.2 ff/ml-years (OR 3.51; 95% CI 1.29, 9.55).
  • The exposure–response slope (100 times the excess relative risk per fiber-year) was 6.1 (95% CI 4.1, 8.1) among all men and 3.3 (95% CI 1.5, 5.0) among male blue-collar workers.
  • In men, the joint effect of smoking and asbestos was more than additive for all lung cancer subtypes and did not deviate from a multiplicative scale.
• The authors' conclusion: The authors concluded that their results in men showed an excess risk of lung cancer and its subtypes at low cumulative exposure levels. They also found a steeper exposure–response slope in this range than at higher, previously studied levels.
• Limitations the authors state:
  • Fiber type and dimensions could not be taken into account, because almost all measurements were made by phase-contrast microscopy.
  • Exposure levels were assigned to job titles rather than measured for individuals, which reduces precision.
  • Residual confounding by other workplace hazards remains possible.
  • Selection bias is possible because blue-collar workers participated less often as population controls.
  • The data are less informative at high doses, because few men were highly exposed.
  • Biased recall of smoking habits cannot be ruled out.
  • Lung cancer subtypes were likely partly misclassified, so the subtype results should be interpreted with caution.

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: Lung Cancer, Meta-Analysis, Asbestos Exposure, Habit, Fiber Year, Odds Ratio, confidence interval, Cumulative Exposure.

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