Our study does not address the possibility that the CHRNA3/4 SNPs exert an independent effect on lung cancer risk, as it has been suggested based on the role these receptors may play in mediating the angiogenic and tumor growth effects of NNK (5). However, these effects may not be critical since similar receptor-mediated effects would be expected from nicotine (which is not a carcinogen), the concentration of which is considerably greater (x 10,000) than NNK. Nevertheless, our data clearly indicate that a simple adjustment for number of cigarettes per day is inadequate to control for smoking dose in studies examining the independent association of these variants with smoking-associated lung cancer.
