Areca nut chewing and esophageal squamous-cell carcinoma risk in Asians: A meta-analysis of case–control studies

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Abstract
This meta-anlaysis quantitatively assessed an overall independent association between areca nut chewing and esophageal squamous-cell carcinoma in Asians. Studies (case–control and/or cohort) were identified by searching the PubMed, Medline, and Embase databases through 30 September, 2012, using the keywords o/esophageal squamous-cell carcinoma, o/esophageal cancer, chewing areca nut, betel quid without tobacco, Asia, and the reference lists of retrieved articles. Random-effects model was used to compute adjusted summary ORRE for the main effect of areca nut chewing and additive (biological) interaction between areca nut chewing and tobacco smoking along with their corresponding 95 % confidence intervals (CI). To quantify the impact of between-study heterogeneity on adjusted main-effect summary ORRE, Higgins’ H and I 2 statistics along with their 95 % uncertainty intervals were used. Funnel plot and Egger’s test were used to evaluate publication bias. Meta-analysis of 12 case–control studies (2,836 cases; 9,553 controls) showed that areca nut chewing was significantly and independently associated with an increased risk of esophageal squamous-cell carcinoma (adjusted main-effect summary ORRE = 3.05; 95 % CI 2.41, 3.87). Furthermore, pooled analysis of additive interaction between areca nut chewing and tobacco smoking reported by six of the included studies revealed manifold increased risk of esophageal squamous-cell carcinoma among those who indulged in both the practices compared with those who practiced none (adjusted additive interaction-effect summary ORRE = 6.79; 95 % CI 4.71, 9.79). There was no significant publication bias (p = 0.289). Areca nut chewing was significantly and independently associated with an increased risk of esophageal squamous-cell carcinoma in Asians. Additionally, individuals who indulged in both areca nut chewing and tobacco smoking had manifold increased risk of esophageal squamous-cell carcinoma. The efforts aimed at curtailing the addiction to areca nut chewing may contribute to lower the incidence of esophageal squamous-cell carcinoma and related mortality in Asians.

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