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The number of studies that have assessed the role of specific genes in smoking behavior continues to grow. The work of Malaiyandi and colleagues (2005), for example, suggests that cytochrome P450 (CYP) 2A6, the liver enzyme which mediates the conversion of nicotine to cotinine, may play an important role in smoking (Malaiyandi et al. 2005). In a review of recent genetic studies of nicotine dependence, Li (2006) presents evidence that several genes may be implicated in nicotine dependence (Li 2006). Some of these genes include gamma-aminobutyric acid 2, which modulates neuronal excitability; nicotinic acetylcholine receptor alpha4, (CHRNA4), which modulates tolerance to nicotine; decarboxylase and brain-derived neurotropic factor, which influence dopamine and serotonin, which play important roles in the reward system of addiction; and the catechol-O-methyltransferase gene, which plays a role in the dopaminergic circuits central to the reward system. These and future studies of the role of genetic influences on smoking have the potential to further the understanding of nicotine addiction and its treatment.

The role of genetics in identifying the best treatment strategies for subgroups of smokers is another important emerging area of research. Pharmacogenetics researchers have examined a variety of polymorphisms and gene variances in smokers and their response to a number of current and widely used cessation pharmacotherapies for nicotine dependence. The results of these studies suggest that specific subgroups of smokers have a significantly higher probability of abstinence when they use nicotine patches, nicotine nasal spray, and bupropion treatment (Lerman et al. 2002, 2004; Swan et al. 2005). However, these studies generally involve small numbers of subjects and the genetic associations need to be replicated. It is expected that continuing research in this area will provide results that can better guide clinicians in selecting the best treatment options for individuals who want to quit smoking and will aid the in development of new drug targets that will help in cessation (Lee and Tyndale 2006).

SMOKING CESSATION

Once the grip of nicotine addiction has taken hold, quitting is hard. Epidemiological data from the 2004 National Health Interview Survey (NHIS) suggest that of the 44.5 million U.S. adults who were current smokers, about 40.5 percent (or 14.6 million) of smokers reported that they had stopped smoking for at least 1 day in the preceding 12 months in an effort to quit (CDC 2005b). Although the number of smokers who attempt to quit is significant, actual quit rates are about 5 percent, and in studies that include biochemical verification of abstention, the actual quit rate is about 3 percent (Shiffman 2004). Some researchers suggest that each year only about 2 percent of smokers will quit permanently (Hughes 2003;



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