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Genetic Determinants of Smoking Cessation

Styn, Mindi Annette (2006) Genetic Determinants of Smoking Cessation. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

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: TaqIA, TaqIB, 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 TaqIA 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 TaqIA was observed.CT screening can create a "teachable moment" for smoking interventions. The association between TaqIA 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.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Styn, Mindi Annettemimst31@pitt.eduMIMST31
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairWeissfeld, Joel L.jwepid@pitt.eduJWEPID
Committee MemberPerkins, Kenneth A.perkinska@upmc.eduKPERKINS
Committee MemberRomkes, MarjorieRomkes@dom.pitt.eduROMKES
Committee MemberLand, Stephanie R.Land@nsabp.pitt.edu
Date: 8 August 2006
Date Type: Completion
Defense Date: 5 May 2006
Approval Date: 8 August 2006
Submission Date: 15 June 2006
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Epidemiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: dopamine receptor; dopamine transporter; lung cancer screening; smoking cessation
Other ID: http://etd.library.pitt.edu/ETD/available/etd-06152006-141415/, etd-06152006-141415
Date Deposited: 10 Nov 2011 19:47
Last Modified: 19 Dec 2016 14:36
URI: http://d-scholarship.pitt.edu/id/eprint/8108

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