Additive Synergism between Asbestos and Smoking in Lung Cancer Risk: A Systematic Review and Meta-Analysis

Our plain-English summary of Additive Synergism between Asbestos and Smoking in Lung Cancer Risk: A Systematic Review and Meta-Analysis, by Y. Ngamwong, W. Tangamornsuksan, O. Lohitnavy, et al (PloS One, 2015).

The study

• Authors: Y. Ngamwong, W. Tangamornsuksan, O. Lohitnavy, N. Chaiyakunapruk, C.N. Scholfield, B. Reisfeld, M. Lohitnavy
• Journal: PloS One
• Published: 2015;10(8):e0135798
• Type of article: Meta-analysis, Systematic review
• Cited by: 62 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Smoking and asbestos exposure are important risks for lung cancer. Several epidemiological studies have linked asbestos exposure and smoking to lung cancer. To reconcile and unify these results, we conducted a systematic review and meta-analysis to provide a quantitative estimate of the increased risk of lung cancer associated with asbestos exposure and cigarette smoking and to classify their interaction. Five electronic databases were searched from inception to May, 2015 for observational studies on lung cancer. All case-control (N = 10) and cohort (N = 7) studies were included in the analysis. We calculated pooled odds ratios (ORs), relative risks (RRs) and 95% confidence intervals (CIs) using a random-effects model for the association of asbestos exposure and smoking with lung cancer. Lung cancer patients who were not exposed to asbestos and non-smoking (A-S-) were compared with; (i) asbestos-exposed and non-smoking (A+S-), (ii) non-exposure to asbestos and smoking (A-S+), and (iii) asbestos-exposed and smoking (A+S+). Our meta-analysis showed a significant difference in risk of developing lung cancer among asbestos exposed and/or smoking workers compared to controls (A-S-), odds ratios for the disease (95% CI) were (i) 1.70 (A+S-, 1.31-2.21), (ii) 5.65; (A-S+, 3.38-9.42), (iii) 8.70 (A+S+, 5.8-13.10). The additive interaction index of synergy was 1.44 (95% CI = 1.26-1.77) and the multiplicative index = 0.91 (95% CI = 0.63-1.30). Corresponding values for cohort studies were 1.11 (95% CI = 1.00-1.28) and 0.51 (95% CI = 0.31-0.85). Our results point to an additive synergism for lung cancer with co-exposure of asbestos and cigarette smoking. Assessments of industrial health risks should take smoking and other airborne health risks when setting occupational asbestos exposure limits.

In plain English

The authors carried out a systematic review and meta-analysis. They pooled 17 earlier studies, 13 found by searching five databases up to May 2015 and 4 from those studies' reference lists: 10 case-control studies with 10,223 participants and 7 cohort studies with 64,924 participants. All asbestos exposure was occupational. People were grouped by asbestos exposure and smoking and compared with a group labelled unexposed non-smokers, which could include people with lower asbestos exposure or lighter smoking. In the case-control studies, the pooled odds ratios were 1.70 (95% CI 1.31–2.21) for asbestos-exposed non-smokers, 5.65 (3.38–9.42) for unexposed smokers and 8.70 (5.78–13.10) for exposed smokers. In the cohort studies, the relative risks were 2.72 (1.67–4.40), 6.42 (4.23–9.75) and 8.90 (6.01–13.18), in the same order. The synergy index was 1.44 (1.26–1.77) for case-control and 1.11 (1.00–1.28) for cohort studies; the multiplicative index was 0.91 (0.63–1.30) and 0.51 (0.31–0.85). The authors concluded there was a positive interaction on an additive scale, an additive synergism, with little evidence of a multiplicative interaction. They noted that exposure measurement and diagnosis varied between studies.

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: Systematic review and meta-analysis of 17 observational studies (10 case-control and 7 cohort studies). Thirteen were found through the database searches and four through the reference lists of retrieved studies.
• Who was studied: Participants of the pooled studies. The 10 case-control studies had 10,223 participants. The 7 cohort studies had 64,924 participants (3,316 cases and 61,608 controls). Studies came from Europe, North America, Australia, China and New Caledonia and were found in databases searched from inception to May 2015.
• Exposure: Occupational asbestos exposure, with or without cigarette smoking. People with lower or shorter fiber exposures were counted as non-exposed, and people with lower cigarette consumption as non-smokers. The included studies also used varying definitions of both.
• Main results:
  • Case-control studies: the pooled odds ratio for lung cancer in asbestos-exposed non-smokers, compared with unexposed non-smokers, was 1.70 (95% CI 1.31–2.21).
  • Case-control studies: the pooled odds ratio in unexposed smokers, compared with unexposed non-smokers, was 5.65 (95% CI 3.38–9.42).
  • Case-control studies: the pooled odds ratio in asbestos-exposed smokers, compared with unexposed non-smokers, was 8.70 (95% CI 5.78–13.10).
  • Cohort studies: compared with unexposed non-smokers, the pooled relative risks were 2.72 (95% CI 1.67–4.40) for asbestos-exposed non-smokers, 6.42 (95% CI 4.23–9.75) for unexposed smokers, and 8.90 (95% CI 6.01–13.18) for exposed smokers.
  • Case-control studies: the synergy index (additive scale) was 1.44 (95% CI 1.26–1.77) and the multiplicative index was 0.91 (95% CI 0.63–1.30).
  • Cohort studies: the synergy index was 1.11 (95% CI 1.00–1.28) and the multiplicative index was 0.51 (95% CI 0.31–0.85).
  • The authors reported a suggestion of a negative multiplicative interaction in both the case-control and the cohort studies.
  • Case-control studies showed high heterogeneity between studies for the smokers-only comparison (I-squared 90.6%) and the exposed-smokers comparison (I-squared 78.7%).
• The authors' conclusion: The authors concluded that the data showed a positive interaction on an additive scale between asbestos exposure and smoking for lung cancer (an additive synergism), with little evidence of an interaction on a multiplicative scale.
• Limitations the authors state:
  • The methods used to measure asbestos and cigarette smoke exposure were arbitrary and varied across studies.
  • The type of asbestos was usually not stated.
  • Studies used different criteria to diagnose lung cancer.
  • The type of lung cancer was rarely stated, nor whether mesothelioma was excluded.
  • Some studies did not provide risk estimates adjusted for age, sex and similar factors.
  • Some case-control studies used controls who had other diseases, most of them also smoking-related.
  • Some data relied on recalling events 10 or more years earlier, raising possible recall bias and misclassification.

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, Systematic Review, Meta-Analysis, Asbestos Exposure, Odds Ratio, Relative Risk, confidence interval.

Related studies

• Absence of synergism between exposure to asbestos and cigarette smoking in asbestosis — J.M. Samet, G.R. Epler, et al. (1979)
• Indirect corrections for confounding under multiplicative and additive risk models — M.H. Gail, S. Wacholder, et al. (1988)
• Exposure to asbestos and the risk of colorectal cancer mortality: a systematic review and meta-analysis — K. Kwak, D. Paek, et al. (2019)
• Risk of mesothelioma after cessation of asbestos exposure: a systematic review and meta-regression — P. Boffetta, F. Donato, et al. (2019)
• Absence of multiplicative interactions between occupational lung carcinogens and tobacco smoking: a systematic review involving asbestos, crystalline silica and diesel engine exhaust emissions — M. El Zoghbi, P. Salameh, et al. (2017)
• Synergy between asbestos and smoking on lung cancer risks — T.C. Erren, M. Jacobsen, et al. (1999)

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