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Interplay of genetic risk (CHRNA5) and environmental risk (partner smoking) on cigarette smoking reduction.

ABSTRACT: BACKGROUND:This study tests whether the genetic predictor (CHRNA5 nicotine receptor gene variants) and an environmental risk factor (partner smoking) interact in the prediction of smoking reduction. METHODS:Subjects were from a community-based, longitudinal study of women (n=1856) who smoked before pregnancy, and a randomized comparative effectiveness smoking cessation trial (n=1065). Smoking reduction was defined as the trajectory of self-reported smoking quantities over time in the observational study, and as the trajectory of alveolar CO levels in the cessation trial. RESULTS:In the pregnancy study, rs16969968 genotype and partner smoking status interacted such that the smoking reduction was lowest for expectant mothers with high genetic risk and partner smoking, and highest for those with high genetic risk but not partner smoking (interaction of genotype×partner smoking on smoking quantity trajectory slope ?=0.071, 95%CI=0.013, 0.13, p=0.017). In the clinical trial, a similar interaction was found (interaction ?=0.20, 95%CI=0.049, 0.36, p=0.010). Furthermore, these associations were moderated by pharmacotherapy such that the interactive relation of genetic and environmental factors occurred in the placebo group, but not in the active pharmacotherapy group (interaction of genotype×partner smoking×pharmacotherapy on CO trajectory slope ?=-0.25, 95%CI=-0.42, -0.091, p=0.0023). CONCLUSIONS:The CHRNA5 genetic risk synergized the effect of partner smoking, producing an especially low likelihood of successful smoking reduction in two complementary studies. This suggests that the genetic vulnerability may be mitigated by altering environmental factors. In addition, cessation pharmacotherapy neutralizes the increase in cessation failure associated with combined genetic and environmental risks, which has possible relevance to treatment algorithms.

SUBMITTER: Chen LS

PROVIDER: S-EPMC4161618 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Interplay of genetic risk (CHRNA5) and environmental risk (partner smoking) on cigarette smoking reduction.

Chen Li-Shiun LS Baker Timothy B TB Piper Megan E ME Smith Stevens S SS Gu Charles C Grucza Richard A RA Smith George Davey GD Munafo Marcus M Bierut Laura J LJ

Drug and alcohol dependence 20140703

<h4>Background</h4>This study tests whether the genetic predictor (CHRNA5 nicotine receptor gene variants) and an environmental risk factor (partner smoking) interact in the prediction of smoking reduction.<h4>Methods</h4>Subjects were from a community-based, longitudinal study of women (n=1856) who smoked before pregnancy, and a randomized comparative effectiveness smoking cessation trial (n=1065). Smoking reduction was defined as the trajectory of self-reported smoking quantities over time in ...[more]

PMID: 25073833

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Project description:ImportanceThe electronic cigarette (EC) has become popular among smokers who wish to reduce their tobacco use levels or quit smoking, but its effectiveness as a cessation aid is uncertain.ObjectiveTo examine the association of regular EC use with the number of cigarettes smoked per day, smoking cessation among current smokers, and smoking relapse among former smokers.Design, setting, and participantsThe CONSTANCES (Consultants des Centres d'Examens de Santé) cohort study, based in France, began recruiting participants January 6, 2012, and is currently ongoing. Participants were enrolled in CONSTANCES through 2015, and included 5400 smokers (mean [SD] follow-up of 23.4 [9.3] months) and 2025 former smokers (mean [SD] follow-up of 22.1 [8.6] months) at baseline who quit smoking in 2010, the year in which ECs were introduced in France, or afterward. Analyses were performed from February 8, 2017, to October 15, 2018.Main outcomes and measuresThe association between EC use and the number of cigarettes smoked during follow-up was studied using mixed regression models. The likelihood of smoking cessation was studied using Poisson regression models with robust sandwich variance estimators. The association between EC use and smoking relapse among former smokers was studied using Cox proportional hazards regression models. All statistical analyses were adjusted for sociodemographic characteristics, duration of follow-up, and smoking characteristics.ResultsAmong the 5400 daily smokers (2906 women and 2494 men; mean [SD] age, 44.9 [12.4] years), regular EC use was associated with a significantly higher decrease in the number of cigarettes smoked per day compared with daily smokers who did not use ECs (-4.4 [95% CI, -4.8 to -3.9] vs -2.7 [95% CI, -3.1 to -2.4]), as well as a higher adjusted relative risk of smoking cessation (1.67; 95% CI, 1.51-1.84]). At the same time, among the 2025 former smokers (1004 women and 1021 men; mean [SD] age, 43.6 [12.1] years), EC use was associated with an increase in the rate of smoking relapse among former smokers (adjusted hazard ratio, 1.70; 95% CI, 1.25-2.30).Conclusions and relevanceThis study's findings suggest that, among adult smokers, EC use appears to be associated with a decrease in smoking level and an increase in smoking cessation attempts but also with an increase in the level of smoking relapse in the general population after approximately 2 years of follow-up.

Dataset Information

Interplay of genetic risk (CHRNA5) and environmental risk (partner smoking) on cigarette smoking reduction.

Publications

Interplay of genetic risk (CHRNA5) and environmental risk (partner smoking) on cigarette smoking reduction.

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