Keeping in mind the above limitations, this study extends previous work on CHRNA5, CYP2A6, and cessation to reach the following conclusions. 1) Nicotine metabolic function estimated via CYP2A6 genotype predicts relapse likelihood in individuals using placebo medication. 2) The effect of pharmacotherapy differs as a function of CYP2A6-based nicotine metabolism. In particular, NRT significantly benefits smokers with fast but not slow nicotine metabolism. The effect of bupropion on relapse likelihood is largely unrelated to CYP2A6 status. 3) The effects of CYP2A6-estimated nicotine metabolism on response to NRT are independent from those of CHRNA5 genotype, with the effects of the two genes being additive. That is, likelihood of benefit from NRT may increase as a function of the combined genetic risks from CYP2A6 and CHRNA5. An important clarification of these pharmacogenetic findings will rely on validation across populations and with different cessation processes such as natural vs. assisted cessation. A larger study or meta-analysis is required to examine the effect of different pharmacotherapies in the combined genetic risk groups. Many other genes have been nominated as predictive of smoking cessation (34),
