Metabolic gene polymorphisms and lung cancer risk in non-smokers: An update of the GSEC study

Sara Raimondi, Paolo Boffetta, Sisko Anttila, Jürgen Bröckmoller, Dorota Butkiewicz, Ingolf Cascorbi, Margie L. Clapper, Tommaso A. Dragani, Seymour Garte, Andre Gsur, Gerald Haidinger, Ari Hirvonen, Magnus Ingelman-Sundberg, Ivan Kalina, Qing Lan, Vera Piera Leoni, Loïc Le Marchand, Stephanie J. London, Monica Neri, Andrew C. PoveyAgneta Rannug, Edyta Reszka, David Ryberg, Angela Risch, Marjorie Romkes, Alberto Ruano-Ravina, Bernadette Schoket, Monica Spinola, Haruhiko Sugimura, Xifeng Wu, Emanuela Taioli

    Research output: Contribution to journalArticlepeer-review


    Background: 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, CYP1A1Ile462Val, 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 CYP1A1Ile462Val polymorphism was observed in Caucasians (adjusted OR = 2.04, 95% CI 1.17-3.54). GSTT1 deletion 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% CI 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 CYP1A1Ile462Val polymorphism may play a role in lung carcinogenesis in Caucasian non-smokers. © 2005 Elsevier B.V. All rights reserved.
    Original languageEnglish
    Pages (from-to)45-57
    Number of pages12
    JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
    Issue number1-2
    Publication statusPublished - 30 Dec 2005


    • Epidemiology
    • Genetic susceptibility
    • Pooled analysis


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