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Cologne Smoking Study (CoSmoS): Teilprojekt „Psychosoziale Analyse“

Leiter der Cologne Smoking Study

Sprecher des Virtuellen Instituts für
Interdisziplinäre Präventionsforschung in der Medizin (VIIRPM)
Prof. Dr. Jürgen Wolf, Centrum für Integrierte Onkologie, Klinik I für Innere Medizin

Leitung des ZVFK-Teilprojekts „Psychosoziale Analyse“

stellvertretender Leiter der Cologne Smoking Study
Prof. Dr. Holger Pfaff

Kooperierende externe Institutionen

GSF, DKFZ, Universität Bonn

Kooperierende Mitgliedseinrichtungen des ZVFK

Prof. Dr. Walter Lehmacher, Institut für Medizinische Statistik, Informatik und Epidemiologie
Weitere beteiligte Wissenschaftler siehe nachfolgenden Text

Operative Projektleitung des ZVFK-Teilprojekts

Dr. Melanie Neumann

Interviewerinnen

Sarah Mostardt


Nazli Sedaghat

Projektzeitraum

09/2004 bis 08/2007

The Cologne Smoking Study (CoSmoS) as the first project of the VIIRPM

Lung cancer and myocardial infarction as the most severe side effects of smoking, but also nicotine addiction itself, are multifactorial diseases triggered by a complex interaction of genetic and environmental risk factors. Taking into account the magnitude of the smoking epidemic and in light of the rather limited success rates of previous anti-smoking programs we strongly believe that it is now a necessity to establish interdisciplinary research networks focusing on the development of novel research concepts to control and prevent smoking-related health risks. We, therefore, have established such an interdisciplinary research team to build the VIIRPM and to propose the Cologne Smoking Study – CoSmoS – with the aim to investigate the role of psychosocial/ behavioural and genetic causes for the development of lung cancer and myocardial infarction in smokers. A national team of experts of classical and genetic epidemiology, social sciences, molecular biology, clinical and translational research has come together to attempt to address the interplay of genetic and environmental factors associated with smoking, with a particular emphasis on nicotine addiction and the risk of lung cancer and myocardial infarction.

We expect to identify populations at highest risk for whom to develop specialized preventive programs in the future.

Several meetings between the members of the network demonstrate the active and lively scientific discussion that has been initiated since spring of 2003. A first example for further synergies and added value beyond the CoSmoS study is the integration of the smoking questionnaire developed within CoSmoS into already existing national structures such as KORA (Kooperative Gesundheitsforschung in der Region Augsburg) cohort, LUCY (lung cancer in the young) and EPIC (European Prospective Investigation into Nutrition and Cancer). This will allow all three projects to partially use data provided by the other studies and will lead to additional information to become available.

The primary goal of CoSmoS is the identification of smokers with high risk to develop lung cancer and/or myocardial infarction. Therefore, among smokers genetic susceptibility for these diseases and the modifying effects of psychosocial factors will be analyzed. In addition, nicotine addiction itself will be characterized with regard to genetic and psychosocial features (and their interaction). Our vision is to use the information from CoSmoS to develop and test risk-stratified programs to prevent smoking-related diseases, in particular lung cancer and MI. This approach distinguishes CoSmoS from previous approaches, since our aim is not to propose and develop general recommendations, but rather to focus on subpopulations based on risk. Two distinct programs are envisioned: first, a risk-adapted program targeting smoking behaviour of young adults, second, risk-adapted nicotine withdrawal programs for adult smokers. We would predict that in addition to changes in environmental factors genetic information will become part of the risk-stratification. These programs will be tested in prospective studies. The development of these prospective evaluations of individualized risk-stratified anti-smoking programs will be initiated already in year two of CoSmoS. For these prospective studies additional funding will have to be applied for. We have already initiated the search for additional partners from behavioural sciences, psychology, educational sciences, medical ethics and health economics.

Summary of the research plan

The overall goal of CoSmoS is the identification and characterization of smokers with high risk to develop lung cancer (LC) and/ or myocardial infarction (MI) as well as an integrated analysis of genetic susceptibility of nicotine addiction. CoSmoS is designed as a case-control study in the Cologne area to identify a high risk population among smokers. Additionally, an explorative part of the study will focus on characterization of smoking habits and nicotine addiction. The first case group will include 1000 LC patients, the second case group 1000 MI patients. A common hospital-based control group (CO) with 1500 patients with diseases not related to smoking will be established. All individuals recruited into the study (cases and controls) will be interviewed and blood will be drawn both for routine biochemical tests from serum and genotyping assays from blood derived DNA and RNA.

Single nucleotide polymorphism analyses of three groups of candidate genes will be performed; these candidate genes are grouped by their potential association with LC, MI or nicotine addiction (NA). In addition to genomic genotyping, skewed allelic expression of the chosen candidate genes will be analysed and tested for association with the three different phenotypes. This will allow to avoid the problem of multiple allelism and raise the power of the association study considerable. Furthermore, the samples will be available for future whole-genome association studies that may be performed if additional funding becomes available. An integral part of CoSmoS is the use of specialized questionnaires including a detailed life-long smoking history, a detailed description of all attempts to quit smoking and the assessment of additional parameters concerning addictive behaviour and life style parameters such as exercise activities and eating habits, but also patho-psychological aspects including anxiety and depression.

A special feature of CoSmoS is the analysis of the influence of psychosocial parameters on genotype – phenotype interactions (effect modification).

Specific Aims

The primary goal of CoSmoS is the investigation of the role of behavioural and genetic causes for lung cancer and/or myocardial infarction in smokers. Furthermore, in an explorative design nicotine addiction will be characterized in current and ex-smokers based on genetic and psychosocial analyses.

Primary questions

Which genetic traits account for the onset of lung cancer and/or myocardial infarction in certain smokers while others are not affected by the disease? Which psychosocial characteristics modify the observed correlations between genotype and disease (effect modification)?

Secondary questions

Which genetic and psychosocial characteristics underly nicotine addiction in smokers (direct and indirect effects)? Which genetic and psychosocial characteristics have an impact on smoking cessation?

  1. focusing on the intention to stop smoking in future

  2. focusing on earlier attempts to quit smoking

Integration into existing structures and networks

 On a national level, the VIIRPM will be networked to three major epidemiological studies, KORA (Kooperative Gesundheitsforschung in der Region Augsburg) and LUCY (Lung Cancer in the Young), both directed by Prof. Wichmann (GSF) as well as EPIC (European Prospective Investigation into Nutrition and Cancer), represented by J. Chang-Claude (DFKZ). Collaborations between J. Wolf, J. L. Schultze and the DKFZ (Abteilung Klinische Epidemiologie) have already been established focusing on the characterization of lung cancer specific expression profiles with a predictive potential. In order to optimize genotyping processing an intense collaboration is scheduled with the Zentrum für Funktionelle Genomforschung (University of Cologne) by Prof. Nürnberg.

 The interaction with the Genetic Epidemiological Methods (GEM) Center Bonn of the National Genome Research Network (NGFN) is provided by Prof. Wienker, who is the PI of GEM Bonn. In Cologne, the competence center for clinical trials (Koordinierungszentrum für Klinische Studien Köln, KKSK) is directly linked to the CoSmoS trial by its head Prof. Lehmacher. Similarly, Prof. Pfaff is head of the Zentrum für Versorgungsforschung Köln (ZVFK) in Cologne thus providing profound expertise in recruitment of hospitalbased controls and conduction of interviews. Prof. Wolf and Prof. Schultze are heading the translational research unit MTBTI (Molecular Tumorbiology and Tumorimmunology), located within the Department of Internal Medicine I at the University Hospital. The MTBTI is also linked to the National Genome Research Network by a project within the Cancer Net of the NGFN 2 program, headed by J. L. Schultze.