Nicotine metabolism as estimated from CYP2A6 genotype predicts both smoking cessation success and differential response to cessation pharmacotherapy. Specifically, fast nicotine metabolism is associated with heightened relapse likelihood with placebo and counseling, and this increased genetic risk was “treated” by cessation pharmacotherapy. Response to NRT differs based on nicotine metabolism. Specifically, active NRT pharmacotherapy is effective among individuals with fast, but not slow estimated nicotine metabolism thereby reducing the risk of faster metabolism with regards to relapse rate. The effect of bupropion on relapse rate, on the other hand, does not differ with estimated nicotine metabolism. We also demonstrated that the effect of CYP2A6 on relapse likelihood remains significant after statistically adjusting for CHRNA5 (a previously reported genetic predictor of cessation (1)). When both genetic risks are combined, how much an individual benefits from NRT depends on his/her combined genetic risk levels of both CYP2A6 and CHRNA5. In our study, the wide variation in number needed to treat (NNT) between smokers with different genetic risks supports the further exploration of pharmacogenetic approaches to smoking treatment.
