We have reported that variation in the nicotine and nitrosamine metabolizing gene, CYP2A6, and the nicotinic receptor subunit gene cluster, CHRNA5-CHRNA3-CHRNB4 (CHRNA5-A3-B4), combined to increase cigarette consumption and lung cancer risk among European American cigarette smokers [1]. The gene discussed is CHRNA5; the disease is lung cancer.