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Methods: Several electronic databases were searched, supplemented by screening reference lists, smoking related websites, and contacting experts. Analytical observational studies of ST use (cohorts, case-control, cross sectional studies) with a sample size of 500 were included if they reported on one or more of the following outcomes (all cause mortality, oral and pharyngeal cancers, other cancers, cardiovascular diseases, dental diseases, pregnancy outcomes, surgical outcomes). Data extraction covered control of confounding, selection of cases and controls, sample size, clear definitions and measurements of the health outcome, and ST use. Selection, extraction and quality assessments were carried out by one or two independent reviewers.
Results: A narrative review was carried out. Many of the studies lacked sufficient power to estimate precise risks, mainly due to the small number of ST users. Studies were often not designed to investigate ST use, and many also had major methodological limitations including poor control for cigarette smoking and imprecise measurements of exposure. Studies in India showed a substantial risk of oral or oropharyngeal cancers associated with chewing betel quid and tobacco. Studies from other regions and of other cancer types were not consistent. Few studies have adequately considered the non-cancer health effects of ST use.
Conclusions: Chewing betel quid and tobacco is associated with a substantial risk of oral cancers in India. Most recent studies from the US and Scandinavia are not statistically significant, but moderate positive associations cannot be ruled out due to lack of power. Further rigorous studies with adequate sample sizes are required, especially for cardiovascular disease.