Areca nut use and cancer in India

Areca nut is widely used in India and the consumption has increased over the past two decades, with availability in new dry packaged forms (pan masala, gutka, mawa). Recent reports of increasing mouth cancer incidence have suggested an association with areca nut consumption. Here we have reviewed the evidence for carcinogenicity of areca nut, including epidemiological studies, several animal studies and mechanistic evidence. Studies primarily from India, providing odds ratios (ORs) or relative risks for precancers or cancer with use of areca nut without inclusion of tobacco is the focus of the review. Six case-control studies on oral submucous fibrosis (OSF) had significantly elevated ORs for use of areca nut in various forms. Six case-control studies on head and neck cancers, primarily oral cancer reported elevated ORs for chewing of betel quid without tobacco. Eight case control studies on oral cancer have reported elevated and significant ORs for betel quid with tobacco. A significant risk in oral cancer was noted in gutka users. Animal studies confirmed correlation between development of precancers or cancers and exposure to areca nut or pan masala without tobacco. Mechanistic evidence shows a role for areca nut alkaloids, polyphenols and copper in promoting carcinogenesis. Our review emphasizes control policies on areca nut products and appropriate mass communication programs for awareness of hazards of areca nut with emphasis on areca nut per se.