Abstract
Smoking is the largest preventable cause of morbidity and mortality in the world. Although there are effective pharmacologic and behavioral treatments for smoking cessation, our inability to objectively quantify smokers’ progress in decreasing smoking has been a barrier to both clinical and research efforts. In prior work, we and others have shown that DNA methylation at cg05575921, a CpG residue in the aryl hydrocarbon receptor repressor (AHRR), can be used to determine smoking status and infer cigarette consumption history. In this study, we serially assessed self-report and existing objective markers of cigarette consumption in 35 subjects undergoing smoking cessation therapy, then quantified DNA methylation at cg05575921 at study entry and three subsequent time points. Five subjects who reported serum cotinine and exhaled carbon monoxide verified smoking abstinence for the 3 months prior to study exit averaged a 5.9% increase in DNA methylation at cg05575921 (p < 0.004) over the 6-month study. Although the other 30 subjects did not achieve smoking cessation at the 6-month time point, their self-reported reduction of cigarette consumption (mean = 6 cigarettes/day) was associated with a 2.8% increase DNA methylation at cg05575921 (p < 0.05). Finally, a survey of subjects as they exited the study demonstrated strong support for the clinical use of epigenetic biomarkers. We conclude that AHRR methylation status is a quantifiable biomarker for progress in smoking cessation that could have substantial impact on both smoking cessation treatment and research.
Highlights
Smoking is the largest cause of preventable morbidity and mortality in the United States
We directly examine the relationship between cigarette consumption status and DNA methylation at cg05575921 in a cohort of subjects undergoing smoking cessation therapy under the direction of their personal physicians
A total of 47 subjects passed the initial screening for inclusion in the study. Four of those subjects were disqualified from further continuation of study for revealing information, such as active cannabis use, during the intake interview that was incompatible with continuation in the study
Summary
Smoking is the largest cause of preventable morbidity and mortality in the United States. Nearly a half-million Americans die secondary to the effects of smoking [1]. Nearly one in every five US adults currently smoke [2]. Three pharmacological agents, bupropion, varenicline, and nicotine replacement therapy (NRT), are commonly used for smoking cessation [3]. Each of these medications is modestly effective and recent clinical trials suggest that the combination of varenicline and NRT is most effective in achieving cessation [3, 4]. The efficacy of these treatments in actual clinical practice has been less than optimal [5]
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