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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