Genetic variation at CHRNA5-CHRNA3-CHRNB4 interacts with smoking status to influence body mass index.

BACKGROUND: Cigarette smoking is associated with lower body mass index (BMI), and a commonly cited reason for unwillingness to quit smoking is a concern about weight gain. Common variation in the CHRNA5-CHRNA3-CHRNB4 gene region (chromosome 15q25) is robustly associated with smoking quantity in smokers, but its association with BMI is unknown. We hypothesized that genotype would accurately reflect smoking exposure and that, if smoking were causally related to weight, it would be associated with BMI in smokers, but not in never smokers. METHODS: We stratified nine European study samples by smoking status and, in each stratum, analysed the association between genotype of the 15q25 SNP, rs1051730, and BMI. We meta-analysed the results (n = 24 198) and then tested for a genotype × smoking status interaction. RESULTS: There was no evidence of association between BMI and genotype in the never smokers {difference per T-allele: 0.05 kg/m(2) [95% confidence interval (95% CI): -0.05 to 0.18]; P = 0.25}. However, in ever smokers, each additional smoking-related T-allele was associated with a 0.23 kg/m(2) (95% CI: 0.13-0.31) lower BMI (P = 8 × 10(-6)). The effect size was larger in current [0.33 kg/m(2) lower BMI per T-allele (95% CI: 0.18-0.48); P = 6 × 10(-5)], than in former smokers [0.16 kg/m(2) (95% CI: 0.03-0.29); P = 0.01]. There was strong evidence of genotype × smoking interaction (P = 0.0001). CONCLUSIONS: Smoking status modifies the association between the 15q25 variant and BMI, which strengthens evidence that smoking exposure is causally associated with reduced BMI. Smoking cessation initiatives might be more successful if they include support to maintain a healthy BMI.

Participation in a population-based physical activity programme as an aid for smoking cessation: a randomised trial.

OBJECTIVES: Exercise combined with nicotine therapy may help smoking cessation and minimise weight gain after quitting. Low participation in vigorous-intensity physical activity programmes precludes their population-wide applicability. In a randomised controlled trial, we tested whether a population-based moderate-intensity physical activity programme increases quit rates among sedentary smokers receiving nicotine therapy. METHODS: Participants (n=481; 57% male; mean age, 42.2 years (SD 10.1); mean cigarette consumption, 27 (SD 10.2) per day) were offered a nine-week smoking cessation programme consisting of a weekly 15-minute counselling session and the prescription of nicotine replacement therapy. In addition, participants in the physical activity group (n=229) also took part in a programme of moderate-intensity physical activity implemented at the national level, and offering nine weekly 60-minute sessions of physical activity. To ensure equal contact conditions, participants in the control group (n=252) attended weekly 60-minute health behaviour education sessions unrelated to physical activity. The primary outcome was continuous CO-verified smoking abstinence rates at 1-year follow-up. RESULTS: Continuous smoking abstinence rates were high and similar in the physical activity group and the control group at the end of the intervention (47% versus 46%, p=0.81) and at 1-year follow-up (27% versus 29%, p=0.71). The mean weight gain after one year was 4.4 kg and 6.2 kg among sustained quitters of the physical activity and control groups, respectively (p=0.06). CONCLUSION: Participation in a population-based moderate-intensity physical activity programme for 9 weeks in addition to a comprehensive smoking cessation programme did not significantly increase smoking cessation rates. A non-significant reduction in weight gain was observed among participants who quit smoking in the physical activity group. TRIAL REGISTRATION: ClinicalTrials.gov; US National Institutes for Health (available online at http://clinicaltrials.gov/; CLINICAL TRIAL REGISTRATION NUMBER: NCT00521391).

Determinants of smoking and cessation in older women

Résumé Introduction : Le tabagisme est le facteur de risque le plus important dans 7 des 14 premières causes de décès chez les personnes de plus de 65 ans. De nombreuses études ont démontré les bénéfices sur la santé d'un arrêt du tabagisme même à un âge avancé. Malgré cela, peu d'actions préventives sont entreprises dans cette population. Le but de ce travail est d'analyser les caractéristiques du tabagisme et de l'arrêt du tabagisme spécifiquement chez les fumeuses d'âge avancé afin de mieux les aider dans leur désir d'arrêter. Méthode : Nous avons évalué les caractéristiques tabagiques au sein d'une étude prospective de 7'609 femmes vivant en Suisse, âgées de plus de 70 ans et physiquement autonomes (étude Semof s'intéressant à la mesure de l'ostéoporose par ultrason osseux). Un questionnaire sur les habitudes tabagiques a été envoyé aux 486 fumeuses éligibles de la cohorte. Leurs stades de dépendance nicotinique et de motivation ont été évalués à l'aide respectivement des scores «Heavy Smoking Index» et « Prochaska ». Les participantes ayant cessé de fumer pendant le suivi ont été questionnées sur, les motivations, les raisons et les méthodes de leur arrêt. Résultats : 424 femmes ont retourné le questionnaire (taux de réponse de 87%) parmi lesquelles 372 ont répondu de façon complète permettant leur inclusion. L'âge moyen s'élevait à 74,5 ans. La consommation moyenne était de 12 cigarettes par jour, sur une moyenne de 51 ans avec une préférence pour les cigarettes dites « légères » ou « light ». Un peu plus de la moitié des participantes avait une consommation entre 1 et 10 cigarettes par jour et la grande majorité (78%) présentait un score de dépendance faible. Les raisons du tabagisme les plus fréquemment évoquées étaient la relaxation, le plaisir et l'habitude. Les principaux obstacles mentionnés : arrêter à un âge avancé n'a pas de bénéfice, fumer peu ou des cigarettes dites light n'a pas d'impact sur la santé et fumer n'augmente pas le risque d'ostéoporose. Le désir d'arrêter était positivement associé avec un début tardif du tabagisme, une éducation plutôt modeste et la considération que d'arrêter est difficile. Durant le suivi de 3 ans, 57 femmes sur 372 (15%) ont arrêté de-fumer avec succès. Le fait d'être une fumeuse occasionnelle (moins de 1 cigarette par jour) et de considérer que d'arrêter de fumer n'est pas difficile était associés à un meilleur taux d'arrêt du tabagisme. Seuls 11% des femmes ayant stoppé la cigarette signalaient avoir reçu des conseils de leur médecin. Conclusion : ces données illustrent le comportement tabagique spécifique des fumeuses d'âge avancé (consommation et dépendance plutôt faibles) et suggèrent que les interventions médicales pour l'aide à l'arrêt du tabagisme devraient intégrer ces caractéristiques. La volonté d'arrêter est associée à un niveau d'éducation plutôt modeste. Les obstacles les plus fréquemment mentionnés sont basés sur des appréciations erronées de l'impact du tabagisme sur la santé.

Nicotine gum treatment before smoking cessation: a randomized trial.

BACKGROUND: New ways of improving the efficacy of nicotine therapy need to be explored. We tested whether starting nicotine polacrilex gum treatment 4 weeks before the quit date improved smoking abstinence rates compared with starting treatment on the quit date. METHODS: An open randomized trial of 314 daily smokers (mean, 23.7 cigarettes/d) enrolled through the Internet and by physicians in Switzerland from November 2005 to January 2007. In the precessation treatment group, participants received nicotine polacrilex gum (4 mg, unflavored) by mail for 4 weeks before and 8 weeks after their target quit date, and they were instructed to decrease their cigarette consumption by half before quitting. In the usual care group, participants received the same nicotine gum for 8 weeks after their quit date and were instructed to quit abruptly. Instructions were limited to a booklet sent by mail and access to a smoking cessation Web site. Results are expressed as self-reported abstinence rates at the end of treatment and as biochemically verified smoking abstinence (cotinine plus carbon monoxide) after 12 months. RESULTS: Eight weeks after the target quit date, self-reported 4-week abstinence rates were 41.6% in the precessation treatment group and 44.4% in the usual care group (P = .61). One year after the target quit date, biochemically verified 4-week smoking abstinence rates were 20.8% in the precessation treatment group and 19.4% in the usual care group (P = .76). CONCLUSION: Starting nicotine gum treatment 4 weeks before the target quit date was no more effective than starting treatment on the quit date.

Convention-cadre pour la lutte antitabac: un instrument puissant de santé publique. [The Framework Convention for Tobacco Control (FCTC): a powerful public health instrument].

The Framework Convention on Tobacco Control (FCTC) isa global and comprehensive legal framework for reducing demand for tobacco (e.g. price measures; ban on smoking in enclosed places; contents of tobacco products; packaging and labeling; advertising, promotion and sponsorship; liability, tobacco cessation, etc.) and supply (e.g. illicit trade; sales to/by minors, etc.). Adopted in 2003, the FCTC has been ratified by 174 countries so far. Switzerland has signed the treaty in 2004 but ratification will necessitate the implementation of stronger tobacco control measures at the national level. The FCTC is a priority of any strategy to reduce noncommunicable diseases in populations. Broad implementation of the FCTC has the potential to prevent a substantial proportion of the billion of tobacco-related deaths expected in the 21st

Conseit aux fumeurs: mise à jour épidémiologique et clinique [Smoking cessation intervention: 2006 update]

Recent Swiss reports confirmed that several chemical products added to cigarettes may increase the level of dependence and therefore the consumption of cigarettes. Observational studies demonstrated the association between smoking and type II diabetes, that smoking one to four cigarettes daily increases significantly the risk of disease and that the relative risk of breast cancer among non smoking women exposed to passive smoking is increased by 30%. The safety of nicotine replacement therapy for patients with cardiovascular disorders has been confirmed. Among new pharmacological approaches, varenicline, rimonabant, topiramate and nicotine vaccine all appear promising.

Smoking, prevalence of disease and health service utilization among the Swiss population.

The data of the 1981-83 Swiss National Health Survey "SOMIPOPS", based on a randomly selected sample of 4,235 individuals aged 20 or over representative of the whole Swiss population, were used to investigate the relation between smoking, prevalence of disease and frequency of health care utilization. The risks of several conditions, including hypertension, myocardial infarction and other heart diseases, asthma, tuberculosis and kidney disease were elevated among ex-smokers. The diseases showing elevated risks among current smokers and significantly positive dose-risk trends included acute bronchitis (relative risk, RR = 3.2 for heavy cigarette smokers vs never smokers), chronic bronchitis or lung emphysema (RR = 2.0), gastro-duodenal ulcer (RR = 1.8) and bone fractures (RR = 1.6). For respiratory conditions, the risk of pipe or cigar smokers was comparable to that of moderate cigarette smokers, whereas for ulcer (RR = 4.1) or fractures (RR = 2.0) the point estimates were even higher than for heavy cigarette smokers. Smokers tended to consult more frequently general practitioners, used more other outpatients services, and were more frequently admitted to hospital during the year preceding the interview. These effects were consistent across strata of age, socio-economic indicators, and persisted after allowance for major identified potential distorting factors. Thus, the results of this survey confirm that smoking is an important cause of morbidity and a major contributory factor to the use of health services.

Smoking and adolescence: Exploring tobacco consumption and related attitudes in three different age groups in Switzerland

The present study constitutes an investigation of tobacco consumption, related attitudes and individual differences in smoking or non-smoking behaviors in a sample of adolescents of different ages in the French-speaking part of Switzerland. We investigated three school-age groups (7th-grade, 9th-grade, and the second-year of high school) for differences in attitude and social and cognitive dimensions. We present both descriptive and inferential statistics. On an inferential level, we present a binary logistic regression-based model predicting risk of smoking. The resulting model most importantly suggests a strong relationship between smoking and alcohol consumption (both regular and sporadic). We interpret this result in terms of both the impact of the actual campaigns and the cognitive processes associated with adolescence.

Smoking trends in Switzerland, 1992-2007: a time for optimism?

Objective To assess trends in smoking status according to gender, age and educational level in the adult Swiss population. Methods Four national health interview surveys conducted between 1992 and 2007 in representative samples of the Swiss population. Results The prevalence of current smokers increased between 1992 and 1997, decreasing thereafter. In 2007, the prevalence of current smokers (32.0% of men and 23.8% of women) was lower than in 1992 (38.4% and 26.7%, respectively). Whereas the prevalence of current + former smoking decreased from 64.5% in 1992 to 59.3% in 2007 among men, it was similar among women during the same period (44.0% in 1992 and 43.9% in 2007). The prevalence of current + former smokers decreased from 47.2% in 1992 to 46.3% in 2007 in the lower education group (no education + primary), from 54.8% to 52.9% in subjects with secondary level education, and from 55.4% to 48.7% in subjects with university level education. The prevalence of current smokers decreased in all age groups. Finally, the amount of cigarette equivalents smoked per day decreased, but the amount of non-cigarette tobacco (alone or in combination with cigarettes) increased for both sexes. Conclusion The prevalence of smoking has been decreasing in the Swiss population, for both sexes and for most age groups and educational levels between 1992 and 2007. The health effects of the change in type of tobacco products consumed await further investigation.

Change in physical activity after smoking cessation: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

AIMS: To estimate physical activity trajectories for people who quit smoking, and compare them to what would have been expected had smoking continued. DESIGN, SETTING AND PARTICIPANTS: A total of 5115 participants in the Coronary Artery Risk Development in Young Adults Study (CARDIA) study, a population-based study of African American and European American people recruited at age 18-30 years in 1985/6 and followed over 25 years. MEASUREMENTS: Physical activity was self-reported during clinical examinations at baseline (1985/6) and at years 2, 5, 7, 10, 15, 20 and 25 (2010/11); smoking status was reported each year (at examinations or by telephone, and imputed where missing). We used mixed linear models to estimate trajectories of physical activity under varying smoking conditions, with adjustment for participant characteristics and secular trends. FINDINGS: We found significant interactions by race/sex (P = 0.02 for the interaction with cumulative years of smoking), hence we investigated the subgroups separately. Increasing years of smoking were associated with a decline in physical activity in black and white women and black men [e.g. coefficient for 10 years of smoking: -0.14; 95% confidence interval (CI) = -0.20 to -0.07, P < 0.001 for white women]. An increase in physical activity was associated with years since smoking cessation in white men (coefficient 0.06; 95% CI = 0 to 0.13, P = 0.05). The physical activity trajectory for people who quit diverged progressively towards higher physical activity from the expected trajectory had smoking continued. For example, physical activity was 34% higher (95% CI = 18 to 52%; P < 0.001) for white women 10 years after stopping compared with continuing smoking for those 10 years (P = 0.21 for race/sex differences). CONCLUSIONS: Smokers who quit have progressively higher levels of physical activity in the years after quitting compared with continuing smokers.

Cytochrome P450 1A2 activity and inducibility: impact of smoking, smoking cessation and genetic polymorphisms

Aims: Cytochrome P4501A2 (CYP1A2) is involved in the metabolism of severaldrugs (clozapine, olanzapine, theopylline, caffeine, etc) and is induced by smoking.This can result in decreased plasma levels of drugs metabolized by thisisoenzyme, causing a decrease in therapeutic response. After quitting smoking,increased plasma levels can lead to adverse effects of the concerned drugs, such asconfusion and seizures, described under clozapine treatment. The present studyaimed to examine the variation of CYP1A2 activity in a large group of smokersbefore and after smoking cessation. Moreover, we aimed to determine whethergenetic polymorphisms of CYP1A2 gene could influence the inducibility ofCYP1A2. Methods: CYP1A2 activity was determined by the paraxanthine/caffeineratio in 194 smokers and in 118 of them being abstinent during a 4-weekperiod. Participants were genotyped for CYP1A2*1F (rs762551), *1D(rs35694136) and *1C (rs2069514) polymorphisms. Results: Smokers had higherCYP1A2 activity (1.55-fold; p < 0.0001). Individual change of CYP1A2 activityafter smoking cessation ranged from 1.0-fold (no change) to 7.3-fold decreasedactivity. In five participants with low initial CYP1A2 activity, an increase wasobserved after smoking cessation. During smoking, CYP1A2*1F (p = 0.005), CYP1A2*1D (p = 0.014), the number of cigarettes/day (p = 0.012), contraceptives use(p < 0.001) and - 163A/- 2467T/- 3860G haplotype (p = 0.002) influencedCYP1A2 activity, while after quitting smoking, CYP1A2*1F (p = 0.017) and contraceptives(p = 0.05) did. No influence of CYP1A2 polymorphisms on the inducibilityof CYP1A2 was observed. Conclusion: Higher CYP1A2 activity wasmeasured in smokers, but with a large interindividual variability of its inductionby smoking. Careful clinical management with the help of therapeutic drug monitoringis therefore needed for patients receiving drugs which are metabolized byCYP1A2, who stop or start smoking. Unidentified genetic variations in theCYP1A2 gene and/or in other genes controlling CYP1A2 activity and other environmentalfactors could be responsible of the observed differences in CYP1A2enzymatic activity and inducibility.

Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers.

We previously used a single nucleotide polymorphism (SNP) in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI) in a Mendelian randomisation analysis. While seeking to extend these findings in a larger sample we found that this SNP is associated with 0.74% lower body mass index (BMI) per minor allele in current smokers (95% CI -0.97 to -0.51, P = 2.00 × 10(-10)), but also unexpectedly found that it was associated with 0.35% higher BMI in never smokers (95% CI +0.18 to +0.52, P = 6.38 × 10(-5)). An interaction test confirmed that these estimates differed from each other (P = 4.95 × 10(-13)). This difference in effects suggests the variant influences BMI both via pathways unrelated to smoking, and via the weight-reducing effects of smoking. It would therefore be essentially undetectable in an unstratified genome-wide association study of BMI, given the opposite association with BMI in never and current smokers. This demonstrates that novel associations may be obscured by hidden population sub-structure. Stratification on well-characterized environmental factors known to impact on health outcomes may therefore reveal novel genetic associations.

Cancer risk in the Swiss HIV Cohort Study: associations with immunodeficiency, smoking, and highly active antiretroviral therapy.

BACKGROUND: Persons infected with human immunodeficiency virus (HIV) have an increased risk for several cancers, but the influences of behavioral risk factors, such as smoking and intravenous drug use, and highly active antiretroviral therapy (HAART) on cancer risk are not clear. METHODS: Patient records were linked between the Swiss HIV Cohort Study and Swiss cantonal cancer registries. Observed and expected numbers of incident cancers were assessed in 7304 persons infected with HIV followed for 28,836 person-years. Relative risks for cancer compared with those for the general population were determined by estimating cancer registry-, sex-, age-, and period-standardized incidence ratios (SIRs). RESULTS: Highly elevated SIRs were confirmed in persons infected with HIV for Kaposi sarcoma (KS) (SIR = 192, 95% confidence interval [CI] = 170 to 217) and non-Hodgkin lymphoma (SIR = 76.4, 95% CI = 66.5 to 87.4). Statistically significantly elevated SIRs were also observed for anal cancer (SIR = 33.4, 95% CI = 10.5 to 78.6); Hodgkin lymphoma (SIR = 17.3, 95% CI = 10.2 to 27.4); cancers of the cervix (SIR = 8.0, 95% CI = 2.9 to 17.4); liver (SIR = 7.0, 95% CI = 2.2 to 16.5); lip, mouth, and pharynx (SIR = 4.1, 95% CI = 2.1 to 7.4); trachea, lung, and bronchus (SIR = 3.2, 95% CI = 1.7 to 5.4); and skin, nonmelanomatous (SIR = 3.2, 95% CI = 2.2 to 4.5). In HAART users, SIRs for KS (SIR = 25.3, 95% CI = 10.8 to 50.1) and non-Hodgkin lymphoma (SIR = 24.2, 95% CI = 15.0 to 37.1) were lower than those for nonusers (KS SIR = 239, 95% CI = 211 to 270; non-Hodgkin lymphoma SIR = 99.3, 95% CI = 85.8 to 114). Among HAART users, however, the SIR (although not absolute numbers) for Hodgkin lymphoma (SIR = 36.2, 95% CI = 16.4 to 68.9) was comparable to that for KS and non-Hodgkin lymphoma. No clear impact of HAART on SIRs emerged for cervical cancer or non-acquired immunodeficiency syndrome-defining cancers. Cancers of the lung, lip, mouth, or pharynx were not observed among nonsmokers. CONCLUSION: In persons infected with HIV, HAART use may prevent most excess risk of KS and non-Hodgkin lymphoma, but not that of Hodgkin lymphoma and other non-acquired immunodeficiency syndrome-defining cancers. No cancers of the lip, mouth, pharynx, or lung were observed in nonsmokers.