Funding Period 2007 - 2010
Genetic factors and gene-environment interactions in permanent coping with heavy smoking: retrospective life course analyses among 1,553 dependent, heavy smokers
Prof. Dr. Hermann Brenner (Principal Investigator)
German Cancer Research Center (Helmholtz Institute)
Dept. of Clinical Epidemiology and Aging Research
Bergheimer Str. 20, 69115 Heidelberg
The vast majority of heavy smokers are nicotine dependent and at the same time carry the largest risk of smoking-associated diseases. Nicotine dependence is believed to be a complex, polygenically and environmentally determined disorder. Heritability of smoking persistence has been estimated to be at least 50%. Recent data suggested that heavy smoking is not only the clinically most relevant, but also the most heritable symptom of nicotine dependence. However, pertinent data from large scale epidemiologic studies with ascertainment of the role of genetic factors and their interactions with personal and environmental factors for long-term success of coping among heavy, dependent smokers are sparse. Such data would though be of utmost importance regarding the development of more effective, tailored smoking cessation therapy. In this study, retrospective cohort analyses will be carried out among 1,553 women and men aged 50-74, who were identified as ever heavy smokers (regular smokers of 21+ cigarettes per day) in the baseline examination of a statewide, population-based cohort study conducted in Saarland in 2000-2002, and of whom 934 at that time had successfully quit for at least two years. Using already available, detailed information on lifetime history of smoking, other lifestyle and sociodemographic factors, major life events, medical data (including family history), and DNA samples from this cohort, the role of genetic factors (SNPs and haplotypes of carefully selected candidate genes), environmental factors and their interaction on successful smoking cessation will be assessed in a retrospective cohort analysis approach using the extended Cox proportional hazards model allowing for time-dependency of environmental factors.