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  • 1
    Keywords: COMBINATION ; Germany ; COHORT ; DISEASE ; DISEASES ; liver ; MORTALITY ; IMPACT ; RISK-FACTORS ; ASSOCIATION ; WOMEN ; CIGARETTE-SMOKING ; MEN ; smoking ; COFFEE ; SERUM ; DETERMINANTS ; GENERAL-POPULATION ; AUSTRIAN ADULTS ; CARDIOVASCULAR-DISEASE MORTALITY
    Abstract: There is increasing evidence that serum levels of the liver enzyme gamma-glutamyltransferase (gamma-GT) are an important predictor of incidence and mortality of various diseases. Apart from alcohol consumption, body mass index and smoking have been found to be associated with serum levels, but little is known about potential interactions of these factors. The aim of this study was to assess the individual and joint impact of alcohol consumption and smoking on levels of gamma-GT, with particular attention to potential differences by sex. The study was based on data of 8465 subjects aged 50 to 74 years, obtained at baseline examination of the ESTHER study, a large population-based cohort study in Germany. Exposure-outcome relationships were assessed in women and men, adjusting for potential confounders by multiple regression. In both sexes, moderate to heavy alcohol consumption (100+ g/week) was associated with 1.7-fold increased odds of elevated gamma-GT (〉 50 IU/L) in reference to nonsmoking alcohol abstainers, whereas smoking by itself was unrelated to gamma-GT. However, when moderate to heavy alcohol consumption was present in combination with heavy smoking, the odds ratios (95% CI) increased to 2.9 (1.1-7.6) in women and to 3.8 (2.2-6.6) in men (test for interaction between alcohol consumption and smoking: P-females = 0.12, P-males = 0.0017). Conclusion: Our results support the notion of a detrimental interaction between cigarette smoking and alcohol consumption as determinants of elevated serum gamma-GT, especially in men. (HEPATOLOGY 2009;49:802-808.)
    Type of Publication: Journal article published
    PubMed ID: 19152425
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  • 2
    Keywords: RECEPTOR ; Germany ; LUNG-CANCER ; COHORT ; DISEASE ; EPIDEMIOLOGY ; HISTORY ; POPULATION ; RISK ; GENE ; GENES ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; SUSCEPTIBILITY LOCUS ; DISTRIBUTIONS ; SUBUNIT ; smoking ; genetic polymorphism ; TOBACCO ; MAPS ; SINGLE ; ADULTS ; GENETIC EPIDEMIOLOGY ; VARIANT ; DEPENDENCE ; SINGLE NUCLEOTIDE POLYMORPHISMS ; SNPs ; GENOTYPE ; HAPLOTYPES ; USA ; smoking cessation ; GENOME-WIDE ASSOCIATION ; GENERAL-POPULATION ; ROBUST ; historical cohort study
    Abstract: Background: Evidence has recently accumulated that single nucleotide polymorphisms in the genetic region encoding the nicotinic acetylcholine receptor subunits alpha-5, alpha-3, and beta-4 are associated with smoking and nicotine dependence. We aimed to determine whether these genetic variations are also predictive of smoking cessation. Methods: Lifetime history of smoking was assessed by questionnaire at enrolment into a large epidemiological study of the German elderly population (ESTHER study). Cox proportional hazards modeling was applied in a retrospective cohort approach to determine the associations of individual polymorphisms and haplotypes with smoking cessation probability in 1446 subjects who reported regularly smoking more than 20 cigarettes at some point in their lives. Results: Given the genotype distributions and number of cessation events observed, the power to detect associations ranged from 54% to 97% for hazard ratios of 1.2 to 1.4 in case of the variant with strongest prior evidence (alpha = .05). Nonetheless, neither individual polymorphisms nor inferred multilocus haplotypes were significantly associated with smoking cessation. Conclusions: Although the robust association of the nicotinic acetylcholine receptor subunit genes investigated with smoking-related phenotypes is an apparent success story of genetic epidemiology, the respective variations seem to exert no relevant influence on smoking cessation probability in heavy smokers in the general population
    Type of Publication: Journal article published
    PubMed ID: 18996504
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  • 3
    Keywords: Germany ; MODEL ; MODELS ; PATHWAY ; DISEASE ; DISEASES ; EPIDEMIOLOGY ; GENE ; GENES ; validation ; COMPLEX ; COMPLEXES ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; FORM ; PERFORMANCE ; HEALTH ; AGE ; SNP ; statistics ; SELECTION ; VALIDITY ; REGRESSION ; SCALE ; SNPs ; USA ; EXTENT ; LOGISTIC-REGRESSION ; Genetic ; CONFIDENCE ; AXON GUIDANCE PATHWAY ; EXTERNAL VALIDATION ; PARKINSON-DISEASE ; PREDICTION ERROR ; RESAMPLING METHODS ; VARIABLE-SELECTION
    Abstract: Background: Examination of the genetic structure of complex diseases by a "genomic pathway approach"-which applies stepwise model selection to sets of more than 1000 polymorphisms in studies of several hundred subjects-has recently been proposed. Models constructed through extensive selection procedures may yield misleading test statistics and measures of predictive performance; we aimed to quantify the extent Of Such problems inherent to stepwise regression on the genomic pathway scale. Methods: We performed permutation analyses and data-splitting approaches using one of the datasets examined in the paper that originally Suggested this approach (n = 536: 1195 SNPs in 22 genes) (Lesnick et al. PLoS Genet. 2007;3:e98). Results: The P values for the genetic effects produced by standard testing severely overestimated file significance, resulting in our example in a standard P value of 3.5 X 10(-69) and a permutation P of 0.003 (95% confidence interval = 0.001 to 0.009). Furthermore, the apparent validity as measured by the area Under the receiver operating characteristic Curve in 90%. training datasets (0.935 [interquartile range = 0.918-0.951]) was extremely overoptimistic when compared with the validity estimated from the excluded 10% validation subsets (0.564 [0.518-0.614]). This validated area under the receiver operating characteristic curve was lower than for models predicting case/control Status Solely from age and sex while excluding any genetic effects (median difference = -0.040 [95%, confidence interval = -0.049 to -0.031]). Conclusions: The application of stepwise model selection oil the genomic pathway scale-at least in the simple form Currently put forward-is prone to yield highly misleading results. We provide pointers to some promising, alternatives. (Epidemiology 2009;20: 500-507)
    Type of Publication: Journal article published
    PubMed ID: 19533849
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  • 4
    Keywords: Germany ; COHORT ; DISEASE ; EPIDEMIOLOGY ; HISTORY ; POPULATION ; RISK ; PATIENT ; IMPACT ; FREQUENCIES ; AGE ; smoking ; HIGH-RISK ; BEHAVIOR ; COMORBIDITY ; MEDICAL HISTORY ; FRAMEWORK ; CARDIOVASCULAR-DISEASE ; CORONARY-HEART-DISEASE ; development ; smoking cessation ; population-based ; CESSATION ; QUIT ; NICOTINE DEPENDENCE ; INTERVENTIONS ; STATE ; 3 ; CONFIDENCE ; INSIGHT ; OLDER ; health-related behavior ; nicotine withdrawal ; PRIMARY-CARE
    Abstract: Background: Much media attention currently focuses on demands from the organized medical profession in Germany for an altered legal framework regarding remuneration for smoking-cessation interventions. With this development, the question whether smoking is an autonomously chosen lifestyle or, alternatively, an addiction constituting a disease in its own right has once again come to the fore of public debate. Methods: In a population-based study in the German state of Saarland, 10 000 persons aged 50 to 74 were questioned about their health-related behavior and medical history. The frequency of attempts to quit smoking, and of the motivation to do so, was analyzed in relation to the total number of smokers in the survey and was stratified with respect to existing illnesses whose cardiovascular risk potential is exacerbated by smoking. Results: Among 1528 persons who were smokers at the beginning of the study, 76% (95% confidence interval [CI]: 73.7%-78.0%) reported having tried to quit at least once. Among smokers with existing high-risk conditions, this figure was higher, reaching 89% (CI: 83.1%-93.0%) in smokers with known cardiovascular disease. Only 11% of the smokers were content with their smoking behavior; 30% said they wanted to cut down, and 59% said they wanted to quit smoking entirely. Conclusions: Most older smokers in Germany would like to quit smoking and have tried to do so repeatedly without success. In particular, high-risk patients with comorbidities, whose number will further increase as the population ages, are highly motivated to quit smoking and would derive major benefit from effective assistance with smoking cessation. The description of smoking as an autonomously chosen lifestyle appears cynical and deserves to be vigorously rejected. Dtsch Arztebl Int 2009; 106(27): 451-55 DOI: 10.3238/arztebl.2009.0451
    Type of Publication: Journal article published
    PubMed ID: 19652767
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  • 5
    Keywords: Germany ; MODEL ; MODELS ; COHORT ; EPIDEMIOLOGY ; POPULATION ; GENES ; PATIENT ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; VARIANTS ; CARE ; HEALTH ; genetics ; smoking ; REPLICATION ; TOBACCO ; SINGLE ; REGRESSION ; VARIANT ; DETERMINANTS ; DEPENDENCE ; SINGLE NUCLEOTIDE POLYMORPHISMS ; CATECHOL-O-METHYLTRANSFERASE ; PHARMACOGENETICS ; GENOTYPE ; EVENTS ; pharmacology ; USA ; smoking cessation ; population-based ; biotechnology ; GENERAL-POPULATION ; NICOTINE DEPENDENCE ; COMT ; Genetic ; CONFIDENCE ; historical cohort study ; PROPORTION
    Abstract: Genome-wide studies have identified single nucleotide polymorphisms associated with smoking behaviour and nicotine dependence. Less is known about genetic determinants of smoking cessation, but rs4680 in COMT has recently been shown to explain a substantial proportion of the variation in cessation in the general population. We attempted to replicate the reported, clinically relevant effect in a population-based retrospective cohort analysis of 1443 ever-heavy smokers, of whom 925 had reached abstinence. In Cox regression models, neither rs4680 nor two polymorphisms nearby were associated with smoking cessation. The adjusted relative cessation rate (95 percent confidence interval) in rs4680 methionine carriers in reference to valine homozygotes was 0.97 (0.83-1.12). The absence of a significant effect of rs4680 in this statistically well-powered study - the 95% confidence interval even excluding the previously reported effect - highlights the need for rigorous replication efforts and suggests that rs4680 genotype should not yet be considered informative for smoking patient care. Pharmacogenetics and Genomics 19:657-659 (C) 2009 Wolters Kluwer Health / Lippincott Williams & Wilkins
    Type of Publication: Journal article published
    PubMed ID: 19584770
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  • 6
  • 7
    Keywords: RECEPTOR ; Germany ; MODEL ; MODELS ; SUPPORT ; COHORT ; DISEASE ; EPIDEMIOLOGY ; POPULATION ; RISK ; GENE ; SAMPLE ; SAMPLES ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; score ; PHENOTYPES ; SUBUNIT ; genetics ; smoking ; REGION ; PHENOTYPE ; VARIANT ; DEPENDENCE ; SINGLE NUCLEOTIDE POLYMORPHISMS ; ADDICTION ; SINGLE-NUCLEOTIDE POLYMORPHISMS ; pharmacogenomics ; pharmacology ; smoking cessation ; EXTENT ; Polymorphism,Single Nucleotide ; GENERAL-POPULATION ; genetic association ; NICOTINE DEPENDENCE ; Genetic ; Determination ; CHRNA4 ; Fagerstrom score ; TOBACCO DEPENDENCE
    Abstract: Polymorphisms in the CHRNA4 gene coding the nicotinic acetylcholine receptor subunit alpha 4 have recently been suggested to play a role in the determination of smoking-related phenotypes. To examine this hypothesis, we conducted a genetic association study in three large samples from the German general population (N-1 = 1412; N-2 = 1855; N-3 = 2294). Five single-nucleotide polymorphisms in CHRNA4 were genotyped in 5561 participants, including 2707 heavily smoking cases (regularly smoking at least 20 cigarettes per day) and 2399 never-smoking controls (〈= 100 cigarettes over lifetime). We examined associations of the polymorphisms with smoking case-control status and with the extent of nicotine dependence as measured by the Fagerstrom test of nicotine dependence (FTND) score (N = 1030). The most significant association was observed between rs2236196 and FTND (P = 0.0023), whereas the closely linked rs1044396 had most statistical support in the case-control models (P = 0.0080). The consistent effect estimates across three independent cohorts elaborate on recently published functional studies of rs2236196 from the CHRNA4 3'-untranslated region and seem to converge with accumulating evidence to firmly implicate the variant G allele of this polymorphism in the intensification of nicotine dependence. The Pharmacogenomics Journal (2009) 9, 219-224; doi: 10.1038/tpj.2009.6; published online 17 March 2009
    Type of Publication: Journal article published
    PubMed ID: 19290018
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  • 8
    Keywords: Germany ; SYSTEM ; smoking ; RE ; ENGLAND
    Type of Publication: Journal article published
    PubMed ID: 18443171
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  • 9
    Keywords: COMBINATION ; Germany ; RISK-FACTORS ; ASSOCIATION ; HEALTH ; OUTCOMES ; ALCOHOL-CONSUMPTION ; REGRESSION ; DETERMINANTS ; aging ; WEIGHT ; ISSUES ; VARIABLES ; outcome ; GAMMA-GLUTAMYL-TRANSFERASE
    Abstract: Background Dichotomisation of continuous variables before analysis has frequently been criticised but, nonetheless, remains a common approach. We were interested in the effects of dichotomisation of an outcome variable when two predictors are examined. Methods Assuming a log-normally distributed continuous outcome, a three-level and a binary independent variable, we evaluated the results that would be obtained by logistic regression after dichotomisation. Different cut-offs, predictor effects and dispersions were examined, with a special focus on interaction terms. Results Depending on the specific parameter combination, dichotomisation introduced sometimes substantial spurious interactions between the two predictor variables regarding their association with the outcome. These interactions could be assigned statistical significance even with modest sample sizes. Real-life data on sex 3 weight as determinants of gamma-glutamyltransferase provided a practical example of these issues. Conclusions The findings presented add a new aspect to the controversy surrounding dichotomisation of continuous variables. Researchers should critically examine whether the validity of their results might be hampered by such phenomena
    Type of Publication: Journal article published
    PubMed ID: 19692723
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  • 10
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    Epidemiology 21 (4), 586-587 
    Keywords: Germany ; EPIDEMIOLOGY ; HEALTH ; aging
    Type of Publication: Journal article published
    PubMed ID: 20539116
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