Journal Article

Meta- and pooled analyses of the effects of glutathione <i>S</i>-transferase M1 polymorphisms and smoking on lung cancer risk

Simone Benhamou, Won Jin Lee, Anna-Karin Alexandrie, Paolo Boffetta, Christine Bouchardy, Dorota Butkiewicz, Jurgen Brockmöller, Margie L. Clapper, Ann Daly, Vita Dolzan, Jean Ford, Laura Gaspari, Aage Haugen, Ari Hirvonen, Kirsti Husgafvel-Pursiainen, Magnus Ingelman-Sundberg, Ivan Kalina, Masahiro Kihara, Pierre Kremers, Loïc Le Marchand, Stephanie J. London, Valle Nazar-Stewart, Masako Onon-Kihara, Agneta Rannug, Marjorie Romkes, David Ryberg, Janeric Seidegard, Peter Shields, Richard C. Strange, Isabelle Stücker, Jordi To-Figueras, Paul Brennan and Emanuela Taioli

in Carcinogenesis

Volume 23, issue 8, pages 1343-1350
Published in print August 2002 | ISSN: 0143-3334
Published online August 2002 | e-ISSN: 1460-2180 | DOI:
Meta- and pooled analyses of the effects of glutathione S-transferase M1 polymorphisms and smoking on lung cancer risk

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Susceptibility to lung cancer may in part be attributable to inter-individual variability in metabolic activation or detoxification of tobacco carcinogens. The glutathione S-transferase M1 (GSTM1) genetic polymorphism has been extensively studied in this context; two recent meta-analyses of case-control studies suggested an association between GSTM1 deletion and lung cancer. At least 15 studies have been published after these overviews. We undertook a new meta-analysis to summarize the results of 43 published case-control studies including >18 000 individuals. A slight excess of risk of lung cancer for individuals with the GSTM1 null genotype was found (odds ratio (OR) = 1.17, 95% confidence interval (CI) 1.07–1.27). No evidence of publication bias was found (P = 0.4), however, it is not easy to estimate the extent of such bias and we cannot rule out some degree of publication bias in our results. A pooled analysis of the original data of about 9500 subjects involved in 21 case-control studies from the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC) data set was performed to assess the role of GSTM1 genotype as a modifier of the effect of smoking on lung cancer risk with adequate power. Analyses revealed no evidence of increased risk of lung cancer among carriers of the GSTM1 null genotype (age-, gender- and center-adjusted OR = 1.08, 95% CI 0.98–1.18) and no evidence of interaction between GSTM1 genotype and either smoking status or cumulative tobacco consumption.

Keywords: CI, confidence interval; GST, glutathione S-transferase; OR, odds ratio

Journal Article.  5557 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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