ABSTRACT

Tobacco smoking is the most important cause of human oral squamous cell carcinoma (SCC) (Schmidt et al. 2004), although betel chewing is an important contributor in some countries (Awang 1988). The presence of tobacco-related carcinogen-DNA adducts, such as adducts with polycyclic aromatic hydrocarbons, has greatly strengthened the link between the development of oral cancer and smoking (Franceschi et al. 1990; Hsu et al. 1997; Hecht 2002; Schmidt et al. 2004). Two cytochrome P450 (CYP) enzymes, that is, CYP1A1 and CYP1B1, are mainly involved in the bioactivation of benzo[a]pyrene, resulting in the most common smoking-related cellular DNA adducts (Nebert et al. 2004; Wen and Walle 2005; Chi et al. 2009). DNA adducts may lead to cancer by causing mutation in genes essential for key functions, including apoptosis, proliferation, and differentiation. Signicantly increased oral cancer risks are also found in heavy drinkers (Franceschi et al. 1990), presumably by facilitating absorption of the tobacco carcinogens.