Tobacco use is the single greatest cause of preventable death and disease in the USA, accounting for close to 450,000 deaths each year [1
]. Smoking is responsible for 80–90% of lung cancers, and is causally linked to laryngeal, oral, pharyngeal, esophageal, gastric, pancreatic, renal, bladder and cervical cancers. It causes cardiovascular and respiratory diseases, and results in numerous perinatal conditions [2
]. Indeed, tobacco use is responsible for more deaths than alcohol, AIDS, car accidents, illegal drugs, murders and suicides combined [2
]. As a consequence, the economic costs of tobacco use are enormous. Between direct healthcare costs due to tobacco-related diseases and indirect costs due to tobacco use (i.e., lost productivity, absenteeism, and recruitment, retention or replacement of workers), the US economy loses almost US$200 billion each year [1
Nevertheless, one of the greatest public health achievements in US history was the substantial reduction in tobacco use over the past 50 years. A combination of enhanced public awareness, the advent of new medications and the implementation of broad public health policies led to the lowering of US adult tobacco use rates from over 50% in 1965 to approximately 20% today [3
]. Yet, the public health community was not able to meet the 12% prevalence target set for the USA in Healthy People 2010, and recent epidemiological surveys of tobacco use show that the rates of smoking in the USA have remained constant over the past 5 years [3
]. It is now widely accepted among experts in the fields of public health and nicotine dependence treatment that further innovations in treatment approaches are needed in conjunction with more forceful public policies if we are to see additional reductions in tobacco use in the USA in the coming decades [5
There are several reasons for the stalled progress in reducing US smoking rates. First, remarkably few smokers interested in giving up utilize formal treatment programs and US FDA-approved medications for nicotine dependence. Studies show that less than half of smokers who are screened for cessation treatment programs go on to attend [7
], and upwards of 60% of smokers prefer to try to give up on their own without any form of cessation product or behavioral treatment [9
]. However, only 3–5% of smokers who try to give up smoking without formal treatment are successful [10
]. Second, there are comparatively few treatment options available for smokers interested in giving up. Currently, there are only three classes of medications to choose from: nicotine replacement therapy (NRT; patch, gum, lozenge, inhaler or nasal spray), bupropion and varenicline. This is a relatively small number of treatment options compared with the variety of medications available to treat many other medical conditions. Finally, only one out of three smokers who utilize FDA-approved medications for nicotine dependence are successful in their attempt to give up [11
]. For these reasons, it is critical that public health researchers continue to identify ways to increase utilization of efficacious treatments for nicotine dependence while national investment is made in the development of new treatment approaches for smoking, with a major priority given to identifying methods to improve the efficacy of existing treatments for nicotine dependence.
Advances in human genomics may offer just such an important step forward. A genetic biomarker model to guide treatment selection for nicotine-dependent smokers interested in giving up offers the promise of significantly improving treatment response rates. Guided by studies that have associated outcomes with variability in both genes that influence the pharmacokinetics and pharmacodynamics of medications, researchers and clinicians may soon be poised to individualize the treatment of nicotine dependence in order to enhance the probability of giving up, maximize cost–effectiveness and prevent exposure to unnecessary treatment-related side effects. In this paper, we discuss the evidence for the heritability of nicotine dependence, summarize the current literature concerning the links between individual genetic variation and nicotine dependence treatment response, and highlight barriers to the translation of research into clinical practice. While we may be several years away from a time when smokers will provide DNA to their physicians or to their local pharmacy to ascertain immediate personalized treatment recommendations, there is good reason to be hopeful that advances in the pharmacogenetic treatment of nicotine dependence will eventually stimulate the next wave of reductions in the rate of smoking in the USA.