Associations of CYP2A6 genotype with smoking behaviors in southern China

Aims To investigate the association of CYP2A6 genetic polymorphisms with smoking‐related phenotypes in Chinese smokers. Design Case‐only genetic association study. Setting Southern China. Participants A total of 1328 Han Chinese smokers who participated in a community‐based chronic disease screening project in Guangzhou and Zhuhai from 2006 to 2007. Measurements All participants answered a structured questionnaire about socio‐demographic status and smoking behaviors and informative alleles were genotyped for the cytochrome P450 2A6 (CYP2A6) gene (CYP2A6*4,*5,*7,*9 and *10). Findings The frequencies of CYP2A6*4, *5, *7, *9 and *10 alleles were 8.5, 1.2, 6.3, 13.5 and 2.4%, which corresponded to 48.9, 15.4, 24.2 and 11.5% of participants being classified as normal, intermediate, slow and poor metabolizers, respectively. Multivariate analyses in male smokers demonstrated that compared with normal metabolizers, poor metabolizers reported smoking fewer cigarettes per day [adjusted odds ratio (OR) = 0.49; 95% confidence interval (CI): 0.32–0.76], started smoking regularly later in life (adjusted OR = 1.55; 95% CI: 1.06–2.26) and, among former smokers, reported smoking for a shorter duration prior to quitting (adjusted OR = 0.33; 95% CI: 0.12–0.94). However, poor metabolizers were less likely to quit smoking and remain abstinent than normal metabolizers (adjusted OR = 0.54; 95% CI: 0.34–0.86). Conclusions Reduced metabolism function of cytochrome P450 2A6 in smokers appears to be associated with fewer cigarettes smoked, later initiation of smoking regularly, shorter smoking duration and lower likelihood of smoking cessation.     

Weight change after smoking cessation using variable doses of transdermal nicotine replacement

OBJECTIVE: Examine weight change in subjects receiving variable doses of transdermal nicotine replacement for smoking cessation. DESIGN: Randomized, double-blind clinical trial. SETTING: One-week inpatient treatment with outpatient follow-up through 1 year. INTERVENTION: This report examines weight change after smoking cessation for 70 subjects randomized to placebo or to 11, 22, or 44 mg/d doses of transdermal nicotine. The study included 1 week of intensive inpatient treatment for nicotine dependence with active patch therapy continuing for another 7 weeks. Counseling sessions were provided weekly for the 8 weeks of patch therapy and with long-term follow-up visits at 3, 6, 9, and 12 months. MEASUREMENTS AND MAIN RESULTS: Forty-two subjects were confirmed biochemically (i.e., by expired carbon monoxide) to be nonsmokers at all weekly visits during patch therapy. Their 8-week weight change from baseline was 3.0±2.0 kg. For these subjects, 8-week weight change was found to be negatively correlated with percentage of cotinine replacement (r=−.38, p=.012) and positively correlated with baseline weight (r=0 .48, p=.001), and age (r=.35, p=.025). Men had higher (p=.003) 8-week weight gain (4.0±1.8 kg) than women (2.1±1.7 kg). Of the 21 subjects who abstained continuously for the entire year, 20 had their weight measured at 1-year follow-up. Among these 20 subjects, 1-year weight change was not found to be associated with gender, baseline weight, baseline smoking rate, total dose of transdermal nicotine, or average percentage of cotinine replacement during the 8 weeks of patch therapy. CONCLUSIONS: This study suggests that higher replacement levels of nicotine may delay postcessation weight gain. This effect is consistent for both men and women. We could not identify any factors that predict weight change with long-term abstinence from smoking. Presented at the American Society of Addiction Medicine 8th national conference on Nicotine Dependence, Toronto, Ont., Canada, October 12–15, 1995. Supported by a grant from Lederle Laboratories, Pearl River, NY.     

Comparative dynamics of four smoking withdrawal symptom scales

Aims To examine the association of person‐specific trajectories of withdrawal symptoms of urge‐to‐smoke, negative affect, physical symptoms and hunger during the first 7 days after smoking cessation with abstinence at end of treatment (EOT) and at 6 months. Design Hierarchical linear modeling (HLM) was used to model person‐specific trajectory parameters (level, slope, curvature and volatility) for withdrawal symptoms. Setting University‐based smoking cessation trials. Participants Treatment‐seeking smokers in clinical trials of transdermal nicotine versus nicotine spray (n = 514) and bupropion versus placebo (n = 421). Measurements Self‐reported withdrawal symptoms for 7 days after the planned quit date, and 7‐day point prevalence and continuous abstinence at EOT and 6 months. Findings In regressions that included trajectory parameters for one group of withdrawal symptoms, both urge‐to‐smoke and negative affect were predictive of abstinence while physical symptoms and hunger were generally not predictive. In stepwise regressions that included the complete set of trajectory parameters across withdrawal symptoms (for urge‐to‐smoke, negative affect, physical symptoms and hunger), with a single exception only the trajectory parameters for urge‐to‐smoke were predictive. Area under the receiver operator characteristic curve was 0.594 for covariates alone, and 0.670 for covariates plus urge‐to‐smoke trajectory parameters. Conclusions Among a number of different withdrawal symptoms (urge‐to‐smoke, negative affect, physical symptoms and hunger) urge‐to‐smoke trajectory parameters (level, slope and volatility) over the first 7 days of smoking cessation show the strongest prediction of both short‐ and long‐term relapse. Other withdrawal symptoms increase the predictive ability by negligible amounts.     

Awareness and use of smoking cessation treatments among diabetic patients.

AIMS: To investigate awareness of pharmacotherapeutic aids to smoking cessation in diabetic cigarette smokers. METHODS: A structured questionnaire-based interview was held by a research nurse individually with consecutively attending cigarette smokers. RESULTS: Of 597 diabetic patients attending a routine clinic, 100 (17%) were current cigarette smokers. Mean (+/-sd) age was 58+/-11 years, 58% were male, and 96% Type 2 diabetic patients. Mean daily cigarette consumption was 16/day, for a mean duration of 35 years. There were 34% who had never heard of nicotine replacement therapy (NRT), and of those who had, only 49% considered it safe with diabetes. Bupropion (Zyban) was unknown to 46%, and of those who knew of it, 39% thought it unsafe in diabetic patients. Only 31% of the group had been previously offered NRT, and 14% bupropion. The NHS Quitline was known of by 84%, but only 8% had used it. CONCLUSIONS: Cigarette smokers with diabetes have poor uptake, awareness and knowledge of NRT and bupropion as aids to smoking cessation. They comprise a high-risk group, for large and small vessel disease, and these findings are therefore of concern. More active education and support for these patients by medical and nursing staff is needed.     

Effect of cigarette smoking on gastric emptying of solids in Japanese smokers: a crossover study using the 13C-octanoic acid breath test

Background Cigarette smoking is associated with an increased risk of peptic ulcer and gastroesophageal reflux disease. Gastric emptying disorders may play a role in the development of these upper gastrointestinal diseases. Thus, studies examining a link between smoking and gastric emptying disorders have clinical relevance. This study was conducted to investigate the effect of smoking on gastric emptying of solids in Japanese smokers.Methods The ¹³C-octanoic acid breath test was performed in eight male habitual smokers on two randomized occasions (either sham smoking or actively smoking). The time vs ¹³CO₂ excretion rate curve was mathematically fitted to a conventional formula of y (t) = m*k*β*e^−k*t*(1 − e^−k*t)^β−1, and the parameters of k and β were determined: under the crossover protocol, a larger (smaller) β indicates slower (faster) emptying in the early phase, and a larger (smaller) k indicates faster (slower) emptying in the later phase. The half ¹³CO₂ excretion time (t_1/2b = −[ln(1 − 2^−1/β)]/k) and the time of maximal ¹³CO₂ excretion rate (t_max = [lnβ]/k) were also calculated. Between the two occasions, k, β, t_1/2b, and t_max were compared by the Wilcoxon signed-rank test.Results After smoking, k was significantly increased. No significant differences were found in β, t_1/2, and t_max between the two occasions.Conclusions The increase in k suggests the acceleration of gastric emptying in the later phase. For the first time, this study has revealed that acute smoking speeds the gastric emptying of solids in Japanese habitual smokers.     

Genetic susceptibility,smoking, obesity and risk of venous thromboembolism

The F5 G1691A (Factor V Leiden) and F2 G20210A (prothrombin) mutations are linked to an increase in the incidence rate of venous thromboembolism (VTE), but their effects are highly variable. We investigated whether the effects of smoking and obesity might explain this variability. In a case‐cohort study including the participants of the Danish Diet, Cancer and Health study, we computed incidence rates and Cox proportional hazard ratios for VTE in individuals with and without the mutations, categorized by weight and tobacco consumption. The sole effect of heavy smoking was 128 extra VTE events per 100 000 person years in individuals with the F5 G1691A mutation versus 59 in individuals without. The sole effect of obesity was 222 extra VTE events per 100 000 person years in individuals with the F5 G1691A mutation, versus 103 in individuals without this mutation; and 705 extra VTE events per 100 000 person years in individuals with the F2 G20210A mutation versus 107 in individuals without this mutation. The F5 G1691A and F2 G20210A mutations conferred increased susceptibility to the unfavourable effects of smoking and obesity on the risk for VTE. Thus, individuals with genetic risk factors for VTE might benefit from maintaining a healthy lifestyle.     

Genetic polymorphisms of the uridine diphosphate glucuronosyltransferase 1A7 and colorectal cancer risk in relation to cigarette smoking and alcohol drinking in a Chinese population

BACKGROUND: The impact of uridine diphosphate glucuronosyltransferase 1A7 (UGT1A7) polymorphisms on genetic susceptibility to digestive system cancer has received close attention since the discovery by Guillemette, the polymorphisms of which may alter enzyme activity. To clarify the allele frequency distribution and its association with risk of colorectal cancer, a population-based case-control study was carried out in Chinese population. METHODS: A total of 140 patients with colorectal cancer and 280 cancer-free frequency-matched controls from a follow-up cohort population established in 1989, were enrolled. For the UGT1A7 polymorphisms analysis, polymerase chain reaction (PCR)-based genotyping techniques including semi-nested PCR, allele-specific PCR and PCR-restriction fragment length polymorphism (RFLP) were developed. RESULTS: The variant allele frequencies in patients and controls were 50.0% and 38.6%, respectively, which were significantly associated with risk of colorectal cancer (odds ratio [OR]: 1.59; 95% confidence interval [CI]: 1.19-2.13). For the variant genotypes analysis, *2/*2 and *3/*3 exhibited a significant association with risk of colorectal cancer (OR: 7.80, 95%CI: 2.66-22.87; OR: 3.47, 95%CI: 1.51-7.97, respectively). Stratification analysis indicated that in previous-current cigarette smoking (cigarette smoking history), current cigarette smoking (current cigarette smoking status), previous-current alcohol drinking (alcohol drinking history) or current alcohol drinking individuals (current alcohol drinking status), the risk developing colorectal cancer increased: OR (95%CI), 2.81 (0.97-8.11), 3.39 (1.19-9.67), 2.89 (0.99-8.46) and 3.14 (1.09-9.09), respectively. CONCLUSIONS: UGT1A7 polymorphisms may have a significant modifying effect on colorectal cancer risk, which may interact with environmental factors, cigarette smoking and alcohol drinking in colorectal carcinogenesis.     

Genetic variants in the serotonin transporter influence the efficacy of bupropion and nortriptyline in smoking cessation

Aims We investigated whether variants in the serotonin transporter gene (SLC6A4) influence smoking cessation rates using antidepressant therapy (i.e. bupropion and nortriptyline). Design Pharmacogenetic (secondary) analysis of a randomized, placebo‐controlled efficacy trial of bupropion and nortriptyline for smoking cessation. Setting Single‐centre study, Maastricht University, the Netherlands. Participants A total of 214 of 255 (84%) current daily smokers participating in a randomized controlled efficacy trial. Measurements Subjects were genotyped for three functional variants in SLC6A4 (5‐HTTLPR, STin2, rs25531). Primary outcome measures were prolonged abstinence from weeks 4–12, 4–26 and 4–52. Secondary outcome measures included 7‐day point prevalence abstinence at weeks 4, 12, 26 and 52. Findings Carriers of the 5‐HTTLPR high‐activity L‐variant had higher prolonged cessation rates with bupropion than placebo [odds ratio (OR) = 1.44, 95% confidence interval (CI) = 1.01–2.05, P = 0.04]. Combining the three variants resulted in increased prolonged cessation rates for both bupropion and nortriptyline among carriers of four to five high‐activity variants (bupropion: OR = 2.00, 95% CI = 1.21–3.29, P = 0.01; nortriptyline: OR = 1.91, 95% CI = 1.02–3.56, P = 0.04). Similar results were found for point prevalence abstinence. Conclusions Bupropion and nortriptyline seem to be more effective in smoking cessation among SLC6A4 high‐activity variant carriers, probably by blocking the increased serotonin transporter activity, thereby increasing serotonin levels. Prospective studies have to assess if this can improve cessation rates when treatment is targeted at individuals based on their genotypes.