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 journalArticle

48 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)45-57
Number of pages13
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume592
Issue number1-2
DOIs
Publication statusPublished - Dec 30 2005

    Fingerprint

Keywords

  • Epidemiology
  • Genetic susceptibility
  • Pooled analysis

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

Cite this

Raimondi, S., Boffetta, P., Anttila, S., Bröckmoller, J., Butkiewicz, D., Cascorbi, I., Clapper, M. L., Dragani, T. A., Garte, S., Gsur, A., Haidinger, G., Hirvonen, A., Ingelman-Sundberg, M., Kalina, I., Lan, Q., Leoni, V. P., Marchand, L. L., London, S. J., Neri, M., ... Taioli, E. (2005). Metabolic gene polymorphisms and lung cancer risk in non-smokers: An update of the GSEC study. Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 592(1-2), 45-57. https://doi.org/10.1016/j.mrfmmm.2005.06.002