Systematic Review and Meta-Analysis of Association of Smokeless Tobacco and of Betel Quid without Tobacco with Incidence of Oral Cancer in South Asia and the Pacific

Abstract

AimThis systematic review and meta-analysis aimed to critically appraised data from comparable studies leading to quantitative assessment of any independent association between use of oral smokeless tobacco in any form, of betel quid without tobacco and of areca nut with incidence of oral cancer in South Asia and the Pacific.MethodsStudies (case control and/or cohort) were identified by searching Pub Med, CINAHL and Cochrane databases through June 2013 using the keywords oral cancer: chewing tobacco; smokeless tobacco; betel quid; betel quid without tobacco; areca nut; Asia, the Pacific and the reference lists of retrieved articles. A random effects model was used to compute adjusted summary ORRE for the main effect of these habits along with their corresponding 95% confidence intervals. To quantify the impact of between-study heterogeneity on adjusted main-effect summary ORRE, Higgins' H and I2 statistics along with their 95% uncertainty intervals were used. Funnel plots and Egger's test were used to evaluate publication bias.ResultsMeta-analysis of fifteen case–control studies (4,553 cases; 8,632 controls) and four cohort studies (15,342) which met our inclusion criteria showed that chewing tobacco is significantly and independently associated with an increased risk of squamous-cell carcinoma of the oral cavity (adjusted main-effect summary for case- control studies ORRE = 7.46; 95% CI = 5.86–9.50, P<0.001), (adjusted main-effect summary for cohort studies RR = 5.48; 95% CI = 2.56–11.71, P<0.001). Furthermore, meta-analysis of fifteen case control studies (4,648 cases; 7,847 controls) has shown betel quid without tobacco to have an independent positive association with oral cancer, with OR = 2.82 (95% CI = 2.35–3.40, P<0.001). This is presumably due to the carcinogenicity of areca nut. There was no significant publication bias.ConclusionThere is convincing evidence that smokeless (aka chewing) tobacco, often used as a component of betel quid, and betel quid without tobacco, are both strong and independent risk factors for oral cancer in these populations. However, studies with better separation of the types of tobacco and the ways in which it is used, and studies with sufficient power to quantify dose-response relationships are still needed.

Global Epidemiology of Head and Neck Cancers: A Continuing Challenge

“…Two thirds of the global burden of these cancer cases occur in developing countries, with the Indian subcontinent accounting for one third of the global burden of cancers of the lip and oral cavity [3] . The incidence rates for cancer of the lip, oral cavity and pharynx (C00-14, excluding C11) as well as the larynx (C32) are increasing among women globally, which could be due to access to better diagnostic aids or changes in the socially acceptable behaviour pattern among women in many other parts of the world such as India [32,33] . Apart from the traditional risk factors discussed above, it has been suggested that oestrogen deficiency may influence susceptibility to oral cancer (C00-06) in women; significantly younger mean age at menopause and higher rates of hysterectomy may influence the high rates of oral cancer reported among younger females [34] .…”

Upregulated expression of MMP-9 in gingival epithelial cells induced by prolonged stimulation with arecoline

“…The association of these components with oral carcinogenesis remains unclear. Areca nut and its component arecoline, a nicotinic acid-based alkaloid, have been reported to promote oral cancer and precancerous lesions (5). Areca nut extract and arecoline induce the upregulation of various growth factors, enzymes and other molecules associated with oral submucous fibrosis, a precancerous condition (6), and stimulate oral cancer cells and immortalized cell lines to express molecules associated with cancer progression (7,8).…”

Clathrin‐mediated endocytosis is required for ANE 30‐100K‐induced autophagy

“…Among these diversified components, AN is the indispensable constituent of BQ, which is also regarded as a human carcinogen . In addition to oral submucous fibrosis, a recent systematic review and meta‐analysis studies showed that AN usage is positively correlated with oral cancer . Thus, mechanisms of AN‐mediated cell responses are important to uncover the pathology of AN‐associated diseases and worthy to be investigated.…”