U p to 75% of oral cavity cancers, 1 the majority of which are squamous cell carcinomas, are thought to be attributable to the separate and combined habits of alcohol drinking, tobacco use and paan (betel-quid) chewing. [2][3][4] In the West, the principal known aetiological factors for oral cancer are tobacco use and alcohol drinking. Epidemiological studies have shown a strong association between the use of tobacco (smoked and chewed) and oral carcinogenesis. [5][6][7] However, alcohol is increasingly being recognised as an important risk factor, having a multiplicative synergistic carcinogenic effect with tobacco. 2,[8][9][10] It has been calculated that a non-drinking heavy smoker (smoking more than twenty per day 11 ) may have a two-to four-fold increased risk of developing squamous cell carcinoma than a non-smoker, whereas a heavy smoker and drinker (drinking over 21 units/week) 12 has a six-to fifteen-times increased risk. 1,13,14 However, the other known risk habit of paan chewing is widespread in the Indian sub-continent, 4 where oral cancer accounts for more than one third of all cancers compared with the prevalence of 3% of all malignancies in Western Europe. Paan use is also prevalent among Asian communities living in the United Kingdom; 15,16 and a higher number of oral and pharyngeal cancers within immigrants of Indian ethnic origin compared with Caucasians has been reported. [17][18][19][20][21] The components of paan can vary between communities and individuals, 22 although the major constituents are the leaf of Piper betel (betel leaf); sliced nut of Areca catechu (areca nut/sopari); lime; catechu (a resinous extract from the wood of the acacia tree); grated coconut and a variety of spices such as aniseed, peppermint, cardamom and cloves. 15,23 The addition of tobacco to paan is associated with a significant risk of oral cancer development. The presence of lime within paan has also been shown to release reactive oxygen species from extracts of areca nut that could contribute to the cytogenetic damage involved in the aetiology of oral cancer. 24 A synergistic increase in oral cancer risk has been shown among people who consume alcohol, smoke and chew paan. 4,25,26 In addition, the chewing of areca nut is associated with the premalignant condition of oral submucous fibrosis especially when used in the form of paan masala. 4,27,28 Paan masala (or guthkha) is a dry complex mixture, with or without tobacco, of areca nut, catechu, lime, cardamom, flavourings and sweetening agents; and is sold and readily available in the UK. Paan masala has been shown to be genotoxic, causing DNA damage via water soluble direct acting mutagens such as the areca nut alkaloids (arecoline, guvacoline, arecadine, guvacine) and tobacco derived nitrosamines found within the mixtures; with mutagenicity being potentiated by the use of ethanol. 23,29 Previous epidemiological studies of cancer incidence and mortality classify 'Asians' together as one group when making comparisons with the Caucasian population. 18,30 However, th...
