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Genetic polymorphisms in dopamine-related genes and smoking cessation in women: a prospective cohort study.

ABSTRACT: Genes involved in dopaminergic neurotransmission have been suggested as candidates for involvement in smoking behavior. We hypothesized that alleles associated with reduced dopaminergic neurotransmission would be more common in continuing smokers than among women who quit smoking.The study included 593 women aged 26-65 years who participated in a twelve month smoking cessation trial conducted in 1993-1994. Participants were contacted three years after the trial to obtain updated smoking history and biological specimens. Seven polymorphisms were assessed in genes involved in dopamine synthesis (tyrosine hydroxylase [TH]), receptor activation (dopamine receptors [DRD2, DRD3, DRD4]), reuptake (dopamine transporter [SLC6A3]), and metabolism (catechol-o-methyltransferase [COMT]). Smoking cessation was assessed as "short-term" quitting (abstinence for the seven days before the conclusion of the trial) and "long-term" quitting (abstinence for the six months before a subsequent interview conducted several years later).We observed no association of any polymorphism with either short- or long-term quitting. Although some relative risk estimates were consistent with weak associations, either the direction of effect was opposite of that hypothesized, or results of the short- and long-term cessation endpoints differed. However, effect modification on smoking cessation was observed between DRD2 Taq1A and SLC6A3 VNTR polymorphisms, DRD3 Ser/Gly and d,1-fenfluramine, and DRD4 VNTR and d,1-fenfluramine.Although these results fail to support prior findings of independent associations of these polymorphisms with smoking status, our exploratory findings suggestive of gene-gene and gene-treatment interactions warrants further investigation.

SUBMITTER: Ton TG

PROVIDER: S-EPMC1865548 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature

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Genetic polymorphisms in dopamine-related genes and smoking cessation in women: a prospective cohort study.

Ton Thanh G N TG Rossing Mary Anne MA Bowen Deborah J DJ Srinouanprachan Sengkeo S Wicklund Kristine K Farin Federico M FM

Behavioral and brain functions : BBF 20070428

<h4>Background</h4>Genes involved in dopaminergic neurotransmission have been suggested as candidates for involvement in smoking behavior. We hypothesized that alleles associated with reduced dopaminergic neurotransmission would be more common in continuing smokers than among women who quit smoking.<h4>Methods</h4>The study included 593 women aged 26-65 years who participated in a twelve month smoking cessation trial conducted in 1993-1994. Participants were contacted three years after the trial ...[more]

PMID: 17466074

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Project description:Relative effectiveness of smoking cessation medications-varenicline, bupropion and nicotine replacement therapy (NRT)-remains unclear among smokers in real-world settings. Evidence in females and smokers with light/moderate nicotine dependence is particularly insufficient. This study compared the effectiveness of varenicline, bupropion or NRT gum relative to NRT patch, in achieving abstinence among recent quitters.In a national smoking cessation program in Taiwan (2012-2015), a cohort of 11,968 participants received varenicline (n = 5,052), bupropion (n = 823), NRT gum (n = 1944) or NRT patch (n = 4,149). The 7-day, 1-month or 6-month point-prevalence was calculated based on self-reported last smoking event via telephone interview after 6 months. Logistic regression modellings estimated odds ratios (OR) and 95% confidence intervals (CI) for achieving abstinence using different modalities (NRT patch as referent). Models included age, sex, education, marital status, geographic region, smoke-years, nicotine-dependence level, medical institution, number of clinic visits and medication use duration. Analyses were further stratified by sex and dependence severity.Participants were predominantly male (83%) with a mean age of 43.7±12.6 years. Varenicline users were more likely than NRT patch users to achieve abstinence, based on 7-day point-prevalence (OR = 1.30, CI: 1.19-1.44), 1-month point-prevalence (OR = 1.36, CI: 1.24-1.50) or 6-month point-prevalence (OR = 1.30, CI: 1.14-1.47). Compared with NRT patch, varenicline was associated with greater odds of being abstinent in women (OR = 1.29, CI: 1.01-1.65), men (OR = 1.31, CI: 1.18-1.46), those with light/moderate dependence (OR = 1.42, CI: 1.24-1.63) or smokers with severe dependence (OR = 1.19, CI: 1.04-1.37), based on 7-day point-prevalence. Differences in effectiveness were not observed between users of bupropion, NRT gum and NRT patch.In smoking cessation clinics in Taiwan, varenicline users reported higher abstinence rates than NRT patch users after 6 months. Women and smokers with light/moderate nicotine dependence may also benefit from varenicline in actual clinical practice.

Project description:Smoking has a well-documented detrimental effect on risk for myocardial infarction and stroke, but less information is available regarding peripheral artery disease (PAD), particularly among women.To prospectively assess the association of current smoking status, cumulative smoking exposure, and smoking cessation with incident symptomatic PAD in women.Prospective cohort study.U.S. female health care professionals in the Women's Health Study.39,825 women with no cardiovascular disease who were prospectively followed for a median of 12.7 years.Incidence of symptomatic PAD. Cox proportional hazards models were used to compare PAD risk across smoking categories.178 confirmed PAD events occurred. Across the 4 smoking categories (never, former, <15 cigarettes/d, and ?15 cigarettes/d), age-adjusted incidence rates were 0.12, 0.34, 0.95, and 1.63 per 1000 person-years of follow-up, respectively. Multivariate adjustment had little effect on this relationship (adjusted hazard ratios [HRs], 3.14 [95% CI, 2.01 to 4.90], 8.93 [CI, 5.02 to 15.89], and 16.95 [CI, 10.77 to 26.67], respectively, vs. women who never smoked). Additional adjustment for high-sensitivity C-reactive protein and soluble intercellular adhesion molecule-1 levels among women with available blood samples (28,314 participants, 117 events) attenuated risk estimates (HR, 5.58 [CI, 2.61 to 11.93] for smoking <15 cigarettes/d and 9.52 [CI, 5.17 to 17.53] for smoking ?15 cigarettes/d). Lifetime exposure showed a strong dose-response relationship; fully adjusted HRs for smoking abstinence of fewer than 10, 10 to 29, and 30 or more pack-years were 2.52 (CI, 1.49 to 4.25), 6.75 (CI, 4.33 to 10.52), and 11.09 (CI, 6.94 to 17.72), respectively. Compared with current smokers, the adjusted HRs for fewer than 10 years, 10 to 20 years, more than 20 years, or lifelong abstinence were 0.39 (CI, 0.24 to 0.66), 0.28 (CI, 0.17 to 0.46), 0.16 (CI, 0.10 to 0.26), and 0.08 (CI, 0.05 to 0.12), respectively.The use of symptomatic PAD as the a priori primary end point excludes asymptomatic disease.Among initially healthy women, smoking is a potent risk factor for symptomatic PAD and was associated with subclinical inflammation. Smoking cessation substantially reduces risk for PAD, but an increased occurrence of PAD persists even among former smokers who maintain abstinence.The National Heart, Lung, and Blood Institute and National Cancer Institute.

Project description:Smoking is associated with an increased risk of total and cause-specific death, but the rate of mortality risk reduction after quitting compared with continuing to smoke is uncertain. There is inadequate or insufficient evidence to infer the presence or absence of a causal relationship between smoking and ovarian cancer and colorectal cancer.To assess the relationship between cigarette smoking and smoking cessation on total and cause-specific mortality in women.Prospective observational study of 104,519 female participants in the Nurses' Health Study with follow-up from 1980 to 2004.Hazard ratios (HRs) for total mortality, further categorized into vascular and respiratory diseases, lung cancer, other cancers, and other causes.A total of 12,483 deaths occurred in this cohort, 4485 (35.9%) among never smokers, 3602 (28.9%) among current smokers, and 4396 (35.2%) among past smokers. Compared with never smokers, current smokers had an increased risk of total mortality (HR, 2.81; 95% confidence interval [CI], 2.68-2.95) and all major cause-specific mortality. The HR for cancers classified by the 2004 surgeon general's report to be smoking-related was 7.25 (95% CI, 6.43-8.18) and 1.58 (95% CI, 1.45-1.73) for other cancers. Compared with never smokers, the HR for colorectal cancer was 1.63 (95% CI, 1.29-2.05) for current smokers and 1.23 (95% CI, 1.02-1.49) for former smokers. A significant association was not observed for ovarian cancer. Significant trends were observed for earlier age at initiation of smoking for total mortality (P = .003), respiratory disease mortality (P = .001), and all smoking-related cancer mortality (P = .001). The excess risk for all-cause mortality decreases to the level of a never smoker 20 years after quitting, with different time frames for risk reduction observed across outcomes. Approximately 64% of deaths among current smokers and 28% of deaths among former smokers were attributable to cigarette smoking.Most of the excess risk of vascular mortality due to smoking in women may be eliminated rapidly upon cessation and within 20 years for lung diseases. Postponing the age of smoking initiation reduces the risk of respiratory disease, lung cancer, and other smoking-related cancer deaths but has little effect on other cause-specific mortality. These data suggest that smoking is associated with an increased risk of colorectal cancer mortality but not ovarian cancer mortality.

Project description:BACKGROUND:The identification of variants in the nicotinic acetylcholine receptor (nAChR) subunit genes associated with smoking phenotypes are increasingly important for prevention and treatment of nicotine dependence. In the context of personalized medicine, the aims of this study were to evaluate whether cholinergic receptor nicotinic alpha 2 (CHRNA2), cholinergic receptor nicotinic alpha 3 (CHRNA3), cholinergic receptor nicotinic alpha 5 (CHRNA5) and cholinergic receptor nicotinic beta 3 (CHRNB3) polymorphisms were associated with nicotine dependence severity, and to investigate possible pharmacogenetics markers of smoking cessation treatment. METHODS:This study cohort enrolled 1049 smoking patients who received pharmacological treatment (varenicline, varenicline plus bupropion, bupropion plus/or nicotine replacement therapy). Smoking cessation success was considered for patients who completed 6 months of continuous abstinence. Fagerström test for nicotine dependence (FTND) and Issa situational smoking scores (Issa score) were analyzed for nicotine dependence. CHRNA2 (rs2472553), CHRNA3 (rs1051730), CHRNA5 (rs16969968 and rs2036527) and CHRNB3 (rs6474413) polymorphisms were genotyped by high resolution melting analysis. RESULTS:Females with GA and AA genotypes for CHRNA5 rs16969968 and rs2036527 polymorphisms had higher success rate in smoking cessation treatment: 44.0% and 56.3% (rs16969968), 41.5% and 56.5% (rs2036527), respectively, compared with carriers of the GG genotypes: 35.7% (rs16969968), 34.8% (rs2036527), (P?=?0.03, n?=?389; P?=?0.01, n?=?391). The GA or AA genotypes for the rs16969968 and rs2036527 were associated with higher odds ratio for success in women (OR?=?1.63; 95% CI?=?1.04 to 2.54; P?=?0.03 and OR?=?1.59, 95% CI?=?1.02 to 2.48; P?=?0.04; respectively). We did not find association of these polymorphisms with nicotine dependence related scores. Polymorphisms in the CHRNA2, CHRNA3 and CHRNB3 genes were not associated with the phenotypes studied. CONCLUSION:CHRNA5 rs16969968 and rs2036527 were associated with higher success rate in the smoking cessation treatment in women. These findings might contribute to advances in personalized medicine.

Dataset Information

Genetic polymorphisms in dopamine-related genes and smoking cessation in women: a prospective cohort study.

Publications

Genetic polymorphisms in dopamine-related genes and smoking cessation in women: a prospective cohort study.

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