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Raimondi S , Boffetta P , Anttila S , Brockmoller J , Butkiewicz D , Cascorbi I , Clapper ML , Dragani TA , Garte S , Gsur A , Haidinger G , Hirvonen A , Ingelman-Sundberg M , Kalina I , Lan Q , Leoni VP , Le Marchand L , London SJ , Neri M , Povey AC , Rannug A , Reszka E , Ryberg D , Risch A , Romkes M , Ruano-Ravina A , Schoket B , Spinola M , Sugimura H , Wu XF , Taioli E
Metabolic gene polymorphisms and lung cancer risk in non-smokers - An update of the GSEC study
Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis. 2005 Dec 30;592(1-2) :45-57
AbstractBackground: Since genetic factors may play an important role in lung cancer development at low dose carcinogen exposure, non-smokers are a good model to study genetic susceptibility and its interaction with environmental factors.Materials and methods: We evaluated the role of the metabolic gene polymorphisms CYP1A1MsPI, CYP1A11le(462) Val, GSTM1, and GSTT1 in non-smoker lung cancer patients from the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC). Non-smokers (defined as subjects who never smoked on a regular basis) were selected from the GSEC database. We pooled the raw data from 21 case-control studies for a total of 2764 Caucasians (555 cases and 2209 controls) and 383 Asians (113 cases and 270 controls). Tests of heterogeneity and of inclusion bias were performed.Results: A significant association between lung cancer and CYP1A11le(462)Val polymorphism was observed in Caucasians (adjusted OR= 2.04, 95% Cl 1.17-3.54). GSTT1 d eletion seems to be a risk factor for lung cancer in Caucasian non smokers only when the analysis was restricted to studies including healthy controls (adjusted OR= 1.66, 95% Cl 1.12-2.46). A protective effect on lung cancer was observed with the combination of CYP1A1 wild type, GSTM1 null, and GSTT1 non-null genotypes. None of the analysed polymorphisms were associated with lung cancer in Asian non-smokers.Discussion: Our analysis confirms previous findings that CYP1A11le(462) Val polymorphism may play a role in lung carcinogenesis in Caucasian non-smokers. (c) 2005 Elsevier B.V. All rights reserved.