Association between Smokeless Tobacco Use and Waterpipe Smoking and the Risk of Lung Cancer: A Systematic Review and Meta-Analysis of Current Epidemiological Evidence

Abstract

Background: Smokeless tobacco and waterpipes are used by hundreds of millions of people worldwide and consumption rates exceed that of cigarette smoking in much of South East Asia and parts of the Middle East. However, the cancer risks of these methods of tobacco consumption are less well-characterized than those of cigarette smoking. The objective of this study was to systematically review the epidemiological evidence on the association between smokeless tobacco use and waterpipe smoking and lung cancer risk.

Methods: The MEDLINE, EMBASE, Web of Science and OpenSIGLE databases were searched to identify eligible case-control and cohort studies (published before 1st December 2020 in any language) that adjusted for cigarette smoking or included non-cigarette smokers only. Summary odds ratio/relative risk estimates and confidence intervals were extracted, and pooled risk ratios (RRs) for lung cancer were calculated using random effects meta-analysis.

Results: The literature search identified 2,465 publications: of these, 26 studies including 6,903 lung cancer patients were included in the synthesis (20 studies of smokeless tobacco use, five of waterpipe smoking, one of both). Our results suggest that smokeless tobacco use is associated with an increased risk of lung cancer among non-cigarette smokers, and that betel quid tobacco may be particularly hazardous. The random effects meta-analysis showed that exclusive use of any type of smokeless tobacco (pooled RR = 1.53, 95%CI 1.09 - 2.14), betel quid chewing (pooled RR = 1.77, 95%CI 1.06 - 2.95), and waterpipe smoking (pooled RR = 3.25, 95%CI 2.01 - 5.25) were significantly associated with an increased risk of lung cancer.

Conclusions: This meta-analysis of case-control/cohort studies supports the hypothesis that use of smokeless tobacco and waterpipe smoking is associated with increased risk of developing lung cancer. Considering the widespread and increasing use of smokeless tobacco in developing countries, and increasing prevalence of waterpipe smoking in almost all societies, these findings inform formulation of public health policy, legislation and tobacco control measures at national and international level to increase awareness and decrease the prevalence of smokeless tobacco use and waterpipe smoking.

Keywords: Tobacco, Smokeless; lung neoplasms; water pipe smoking.

Figure 1

Random Effects Meta-Analysis of the Association between Ever Use of Smokeless Tobacco and Lung Cancer among Non-Smokers. The ORs fore each study are presented as squares, with the position of the square corresponding to the point estimate and the 95% CI shown by horizontal lines. (95% Cis for each study shown in the forest plot are obtained by back transformation using the calculated standard error shown in the analysis and do not always conform exactly to the stated confidence intervals in the paper). The area of the square Is inversely proportional to the variance in the OR. The diamond represents the pooled OR and it’s 95% CI

Figure 2

Random Effects Meta-Analysis of the Association between Ever Use of Betel Quid/Tobacco Mixes and Lung Cancer. The ORs fore each study are presented as squares, with the position of the square corresponding to the point estimate and the 95% CI shown by horizontal lines. (95% Cis for each study shown in the forest plot are obtained by back transformation using the calculated standard error shown in the analysis and do not always conform exactly to the stated confidence intervals in the paper). The area of the square Is inversely proportional to the variance in the OR. The diamond represents the pooled OR and it’s 95% CI

Figure 3

Random Effects Meta-Analysis of the Association between Ever Use of Smokeless Waterpipe Smoking and Lung Cancer. The upper limit for one of the included studies65 was altered as we believe that the value reported in the paper is a typographical error. The CI reported in the published paper is 1.2 – 7.6 and we changed the upper limit to 27.6 to make the CI log symmetrical. We attempted to contact the authors to confirm this but were unsuccessful. The ORs fore each study are presented as squares, with the position of the square corresponding to the point estimate and the 95% CI shown by horizontal lines. (95% Cis for each study shown in the forest plot are obtained by back transformation using the calculated standard error shown in the analysis and do not always conform exactly to the stated confidence intervals in the paper). The area of the square Is inversely proportional to the variance in the OR. The diamond represents the pooled OR and it’s 95% CI