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

Research output: Contribution to journalArticle

  • External authors:
  • 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
  • Agneta Rannug
  • Edyta Reszka
  • David Ryberg
  • Angela Risch
  • Marjorie Romkes
  • Alberto Ruano-Ravina
  • Bernadette Schoket
  • Monica Spinola
  • Haruhiko Sugimura
  • Xifeng Wu
  • Emanuela Taioli

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. © 2005 Elsevier B.V. All rights reserved.

Bibliographical metadata

Original languageEnglish
Pages (from-to)45-57
Number of pages12
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume592
Issue number1-2
DOIs
Publication statusPublished - 30 Dec 2005