November 1, 2002
Genetic Variant May Impact Smoking
Cessation
(Philadelphia,
PA) Smokers with a specific genetic variant may be more
vulnerable to cigarette cravings and relapse when trying
to quit smoking, a study by researchers from the
Tobacco Use Research Center of the University of Pennsylvania
School of Medicine indicates. This study also shows
that the anti-depressant drug bupropion - better known
by its brand name, Zyban® - may lessen these effects,
especially among females. The study, titled "Pharmacogenetic
Investigation of Smoking Cessation Treatment,"
appears in the November issue of Pharmacogenetics.
While previous research has shown that bupropion is
an effective smoking cessation aid, smokers experience
variability in response to this drug and only 30-45
percent remain abstinent. By identifying the genetic
factors that influence response to bupropion, researchers
hope to aid in the development of more effective treatment
strategies that are tailored to individual smokers.
Lead author Caryn Lerman, Ph.D., Associate Director
for Cancer Control and Population Science at the Abramson
Cancer Center of the University of Pennsylvania
and Professor in Penn's School of Medicine and
the Annenberg Public Policy Center, led a research
team that examined 426 smokers enrolled in a randomized
clinical trial of bupropion for smoking cessation. Participants
all provided blood samples and received bupropion or
placebo plus seven sessions of behavioral group counseling.
Smoking status, abstinence symptoms and side effects
were recorded weekly, and smoking status was verified
at the end of treatment and again at a six-month follow-up
appointment.
The researchers found that participants with a decreased
activity variant of the CYP2B6 gene reported
greater increases in cravings for cigarettes following
the quit date and were about one and a half
times more likely to relapse during the treatment phase.
"This study provides an important first step
toward utilizing genotype to identify smokers who are
more vulnerable to relapse and who may benefit most
from more intensive smoking cessation treatment,"
said Lerman.
In previous research, the CYP2B6 enzyme (the
product of this gene) has been found to affect both
nicotine metabolism and bupropion metabolism. Lerman
and her colleagues speculate that the effect of the
genetic variant on cessation may be due to inherited
differences in nicotine metabolism. "Brain concentrations
of human CYP2B6 may alter local metabolism of
nicotine. Such effects could contribute to neuroadaptations
that alter the subjective effects of abstinence from
smoking, thereby promoting relapse," said Lerman.
The present data do not suggest that the CYP2B6
genetic effect on smoking cessation is attributable
to individual differences in bupropion metabolism; however,
further research in this area is needed.
The study also provides preliminary evidence that bupropion
may help smokers, especially females, overcome the effects
of genetic predisposition on relapse rates. Among women
with the CYP2B6 polymorphism, 54 percent of those
who were treated with bupropion were abstinent at the
end of treatment, compared with 19 percent of those
who received placebo. The researchers believe that this
difference might be due to bupropion's effect on abstinence-induced
negative moods that are more common among women.
This research was funded by the National Cancer Institute
and the National Institute on Drug Abuse and was conducted
by the University of Pennsylvania/Georgetown University
Transdisciplinary Tobacco Use Research Center.
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