- To investigate the role of passive smoking and other environmental exposures in the causation of lung cancer among non smokers, particularly by assessing low levels of exposure using biomarkers of exposure.
- To study the role of genetic polymorphism of cytochrome P450 enzymes and of DNA repair activity in non-smokers and its interaction with exposure to environmental carcinogens.
- To study the role of markers of carcinogenic mechanism (intermediate endpoints) in lung carcinogenesis among non-smokers.
Non-smokers represent a very important population to investigate the carcinogenic effect on the lung of low level exposure to environmental carcinogens, the role of genetic predisposition to cancer and the interaction between these two factors.
Among the known or suspected causes of lung cancer in non-smokers are environmental tobacco smoke, dietary factors, occupational exposures, as well as other lung carcinogens present in the general environment. In the proposed study, biological markers of exposure (protein adducts with metabolites of tobacco specific nitrosamines), mechanism of carcinogenesis (activation of ras proto-oncogenes and inactivation of p53 tumoursuppressor genes) and genetic susceptibility (DNA repair activity and polymorphism to metabolic enzymes, such as p450 CYPlAl and 2D6, and GSTl) will be investigated on blood and lung tissue samples from 120 non-smoking lung cancer cases, and the same number of smoking lung cancer cases and of non-smoking controls, who will be enrolled in six participating centres (Bremen, Munich, Turin, Padua, Rome, Paris).
Each subject will be interviewed according to the questionnaire focused on active smoking, environmental tobacco smoking and other environmental and occupational exposures as well as on genetic factors.
Validation of non-smoking status will be carried out by re-interviews to next of kin of non-smokers and measurement of urinary cotinine levels. The multivariate data analysis will consist of two sets of comparisons: the presence/level of markers will be compared between non-smoking lung cancer cases and non-smoking controls, to evaluate the role of the markers in predicting the risk of lung cancer, at a given level of exposure to environmental carcinogens, and the presence/level of markers will be compared between non-smoking and smoking lung cancer cases, to evaluate the role of markers in smoking and non-smoking-related lung cancer.
Funding SchemeCSC - Cost-sharing contracts