Genetics May Determine Success in Smoking Cessation
The Center for Disease Control and Prevention estimates that 46 million Americans are current smokers, and that 443,000 deaths are caused by cigarette smoking every year. Almost 70% of smokers wish to quit, but only an average of 5% are able to successfully quit on their own, and 25% quit with nicotine replacement therapy. Smoking remains to be the leading preventable cause of death in the U.S. Facing such grueling odds, researchers from the National Institute on Drug Abuse (NIDA) and Duke University’s Center for Nicotine and Smoking Cessation Research and Department of Psychiatry conducted a new research study comparing the genotypes of various smokers to discover the genetic variant associated with successful smoking cessation.
The researchers proclaim that customized nicotine replacement therapy (NRT) dosages that are based off a smoker’s level of nicotine dependence and genotype can significantly improve their chances of successful smoking cessation. Those with higher nicotine dependence may require higher doses of NRT both before and after their quit dates, while those with lower nicotine dependence may need a lower dose of NRT. Furthermore, the extent of a certain chromosomal region in participants’ bloodstream—which researchers rated using a “quit-success” genotype score—may determine those who are more genetically predisposed to abstinence.
Researchers tested 479 cigarette smokers who wished to quit and divided them into two groups based on their level of nicotine dependency. Using the Fagerstrom Test for Nicotine Dependence, participants’ level of nicotine dependency was classified as either low or high based on their scores (on a scale of 0–10, with anything below 6 considered “low” and anything 6 or higher considered “high”). Participants from half of each group were administered the traditional NRT method, which involves a 21-mg nicotine patch in the morning followed by a placebo patch in the afternoon, and the other halves of the groups were administered two 21-mg nicotine patches (42-mg) worn for 24 hours. NRT with two patches daily and use of denicotinized cigarettes for all participants was initiated two weeks prior to participants’ quit date. Then, the same nicotine patch therapy alone continued for 4–6 weeks after the quit date. Nicotine dosages were gradually reduced over another 4–6 weeks (totaling a 10–12 week study).
During the study, participants gave DNA samples for researchers to determine their genotyping in a blind research. Participants’ “quit-success” genotype scores were measured by assessing alleles in 12,058 single nucleotide polymorphisms (SNPs) that have been proven to be associated with successful smoking cessation in previous studies. Based on the SNPs’ strength and replicability, the “quit-success” genotype scores were classified as either low (less than or equal to the median) or high (greater than the median).
As a result, researchers found that a three-way interaction was taking place between the nicotine dose, level of nicotine dependency, and “quit-success” genotype score. First, the higher dose (42-mg) NRT regimen improved abstinence in participants with high dependence and low “quit-success” genotype scores. However, the 42-mg dose NRT regimen given to participants with low dependence and low “quit-success” genotype scores had reduced their ability to abstain. Instead, those participants with low dependence, low “quit-success” genotype scores, and low dose (21-mg) NRT achieved abstinence significantly more. For those participants with the high “quit-success” genotype scores, abstinence was best achieved with the lower dose (21-mg) NRT despite their level of dependence. In fact, individuals with the higher “quit-success” genotype scores did not especially benefit from taking the higher dose (42-mg) NRT in their effort to abstain.
Using individuals’ “quit-success” scores and level of nicotine dependency, doctors may be able to better treat their patients by matching their genetics and physiology to the appropriate level of NRT. The innovative, three-way, individualized abstinence approach—level of nicotine dependence, “quit success” genotype score, and nicotine dose—is what the researchers are hoping will become a new standard in smoking cessation therapy.
Source: Department of Psychiatry and Center for Nicotine and Smoking Cessation Research, Personalized Smoking Cessation: Interactions between Nicotine Dose, Dependence and Quit-Success Genotype Score, July-August 2010
