Promise of Pharmacogenomics in Smoking Cessation

Abstract

Individual differences in the ability to quit smoking provide an important model for ‘higher order’ pharmacogenomics. Twin studies document strong, ca 0.5 heritability for success in smoking cessation [1,2]. This behavior change yields sizable health benefits. Smoking remains one of the largest preventable causes of death, causing more than 400,000 premature US deaths per year [3]. Many of these deaths could have been deferred by successful midlife cessation, even in individuals who have smoked for years prior to quitting. While many smokers attempt to quit each year, only approximately one in ten or one in 20 are able to remain abstinent [4]. This rate can be augmented twoor more-fold by treatments that target the brain nicotinic acetylcholine receptors at which nicotine (nicotine replacement or varenicline), or the dopamine transporter (bupropion) exerts its effect. Nevertheless, the odds that a smoker who attempts to quit will relapse are still much greater than the chances that he will achieve and maintain abstinence. Improving these odds is a major goal of academic and pharmaceutical therapeutic development programs, and a promising setting in which thoughtfully applied pharmaco genomics could provide substantial health improvements with favorable cost:benefit ratios. Pharmacogenomics’ promise for smoking c essation includes: