| Current findings related to nicotine addiction and related physiologic-metabolic processes create a biological basis to consider the role of interindividual genetic differences governing smoking behavior.;This study examined associations between smoking cessation and a set of potential risk factors measured in a group of adult cigarette smokers participating in a computed tomography (CT) lung cancer screening program. The investigation of non-genetic factors focused on the relationship between CT results and smoking cessation. The investigation of genetic factors attempted to determine genetic influences on the relationship between the dopamine pathway and smoking cessation by examining genetic variation in the dopamine receptor 2 ( DRD2: TagIA, TagIB, C957T, -141C Ins/Del) and dopamine transporter (SLC6A3).;Participants were part of the Pittsburgh Lung Screening Study (PLuSS), a research based low-dose CT screening program containing current and former cigarette smokers, ages 50 to 79. These analyses were restricted to baseline smokers who indicated their smoking status at follow up. Non-genetic factors were assessed for all eligible members of the cohort; genetic factors were assessed for a subset.;A CT scan of the lungs that resulted in a referral was significantly associated with abstinence (for more than 30 days) at one year. The relative risk of being abstinent at one year after receiving a CT referral was 1.39 (95% Confidence Interval (CI): 1.14-1.70). After controlling for the matching variables and other genotypes, the DRD2 TagIA polymorphism was significantly associated with being abstinent at one year (p=0.01). Compared to participants with the A2A2 genotype, participants who carried at least one variant allele (A1) were less likely to be abstinent (Odds Ratio: 0.47, 95% CI: 0.24-0.94). SLC6A3 genotype was not associated with abstinence at one-year (p=0.757). No significant gene-gene interaction with TagIA was observed.;CT screening can create a "teachable moment" for smoking interventions. The association between TagIA and abstinence at one year supports the hypothesis that genetic variation in the dopamine pathway influences smoking cessation.;Public Health Significance: Smoking is the leading preventable cause of death in the United States. Identifying genetic variations that influence smoking behaviors could enhance treatment options for smoking cessation. This dissertation identified both non-genetic and genetic influences on smoking cessation. Consideration of those influences in the selection of quitting regimens may improve success rates thereby reducing the morbidity and mortality due to continued cigarette smoking. |
