DESCRIPTION (Adapted from the Applicant's Abstract): Cigarette smoking remains
the single most preventable cause of cancer mortality in the United States.
However, although most current smokers report a desire to quit, the decline in
adult use of tobacco has slowed in recent years. These observations highlight
the need for new insights into determinants of smoking cessation. Available
data support a role of genetic influences on smoking behavior; these effects
may be most evident in populations, such as the United States, with relatively
strong social pressures against smoking.
The goal of the proposed study is to examine genetic influences on smoking
cessation. Among 700 female participants in a smoking cessation trial, we will
assess the relation of polymorphisms of genes involved in the neurologic
activity or metabolism of tobacco and nicotine with the likelihood of being a
non-smoker at the end of the trial and when re-contacted several years later.
Of particular interest are genes involved in dopaminergic neurotransmission in
the mesolimbic "reward" pathway of the brain, as the addictive effects of
tobacco and nicotine operate primarily through this system. Blood specimens
collected in the proposed study will, in addition to enabling the work
currently proposed, form a resource for future genetic studies of smoking
cessation as new and relevant polymorphisms are identified and characterized.
Increased understanding of genetic influences on the ability of motivated,
healthy individuals to quit smoking may lead to improvements in success rates
of smoking cessation efforts. In the future, such knowledge may allow the
identification of subgroups of individuals who are most likely to benefit from
particular pharmacologic interventions.
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