As ligand-gated ion channels consisting of five subunits, nicotinic receptors are the primary targets for nicotine that initiate the brain responses to smoking. It is biologically plausible, therefore, that these genes may influence smoking intensity and nicotine dependence. However, nicotine-mediated activation of these receptors in vitro has been shown to stimulate cellular proliferation and to inhibit apoptosis of bronchial epithelial cells (13), raising the possibility that nicotine exposure could influence lung cancer directly rather than through the exposure to carcinogenic compounds in cigarette smoke. Thus, biologically plausible mechanisms could explain a direct influence of variation in nicotinic receptors on smoking behaviors a direct or indirect influence on lung cancer risk.
