Genetic variation affects smoking cessation treatment

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Mark Twain boasted that it was easy to quit smoking because he did it every day. We now may have the beginnings of understanding why some people find it so difficult to stop smoking even when they are in treatment for this problem. According to statistics provided by the Centers for Disease Control and Prevention (CDC), tobacco use is the leading preventable cause of death in the United States, and it is the second major cause of death in the world according to the World Health Organization (WHO).

An estimated 20.9% of all US adults smoke, and even with a strong desire to quit, most find it exceptionally difficult. A new study being published in the September 15th issue of Biological Psychiatry reports that genetic variation in a particular enzyme affects the success rates of treatment with bupropion, an anti-smoking drug.

Lee and colleagues performed CYP2B6 genotyping on smoking individuals, a gene that is known to be highly variable and whose enzyme metabolizes both bupropion and nicotine. Participants were then provided with either placebo or bupropion treatment for ten weeks.

The authors discovered that individuals with the CYP2B6*6 allele of the gene benefited from bupropion treatment and maintained abstinence longer while doing poorly on placebo, with a 32.5% abstinent rate vs. 14.3%, respectively. In contrast, those in the CYP2B6*1 group did well on both bupropion and placebo, with similar abstinence rates at the end of treatment and after a six month follow-up.

Rachel Tyndale, M.Sc., Ph.D., one of the authors on this study, comments, “This first study, while requiring replication, identifies a very common genetic variant that appears to affect smoking cessation treatment outcome.” This variant is present in 25-50% of people, thus affecting a large portion of the population.

John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, adds his thoughts about this exciting new data: “We look forward to the era of personalized medicine, when doctors are able to use genetic information about their patients to guide treatment. We are not ready to use this information in clinical practice, but this study provides us with a good example of the type of information that might, some day, guide the treatment for smoking.”

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Notes to Editors:

The article is “CYP2B6 Genotype Alters Abstinence Rates in a Bupropion Smoking Cessation Trial” by Anna M. Lee, Christopher Jepson, Ewa Hoffmann, Leonard Epstein, Larry W. Hawk, Caryn Lerman and Rachel F. Tyndale. Drs. Lee, Hoffmann, and Tyndale are affiliated with the Centre for Addiction and Mental Health and the Department of Pharmacology at The University of Toronto in Ontario, Canada. Drs. Jepson and Lerman are with the Department of Psychiatry at Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania. Dr. Epstein is with the Department of Pediatrics, while Dr. Hawk is with the Department of Psychology at The University of Buffalo, State University of New York, Buffalo, New York. This article appears in Biological Psychiatry, Volume 62, Issue 6 (September 15, 2007), published by Elsevier.

This work was supported by a Canadian Tobacco Control Research Initiative student grant 16803 (AML), Canadian Institute of Health Research (CIHR) Tobacco Use in Special Populations Fellowship (AML), grants from the National Cancer Institute and National Institutes on Drug Abuse, P5084718, RO1 CA63562 (CL) and DA020830 (RFT, CL), CIHR grant MOP53248 (RFT), and a Canada Research Chair in Pharmacogenetics (RFT). Study medication was provided at no cost by GlaxoSmithKline.

Contact: Jayne Dawkins

215-239-3674
Elsevier

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