title: Meta- and pooled analyses of the effects of glutathione S-transferase M1 polymorphisms and smoking on lung cancer risk.
abstract: 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.
authors.affiliation: INSERM U521, EMI 00-06, Evry, France. benhamou@evry.inserm.fr
authors.forename: Simone
authors.initials: S
authors.lastname: Benhamou
authors.forename: Won Jin
authors.initials: WJ
authors.lastname: Lee
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Alexandrie
authors.forename: Paolo
authors.initials: P
authors.lastname: Boffetta
authors.forename: Christine
authors.initials: C
authors.lastname: Bouchardy
authors.forename: Dorota
authors.initials: D
authors.lastname: Butkiewicz
authors.forename: Jurgen
authors.initials: J
authors.lastname: Brockmöller
authors.forename: Margie L
authors.initials: ML
authors.lastname: Clapper
authors.forename: Ann
authors.initials: A
authors.lastname: Daly
authors.forename: Vita
authors.initials: V
authors.lastname: Dolzan
authors.forename: Jean
authors.initials: J
authors.lastname: Ford
authors.forename: Laura
authors.initials: L
authors.lastname: Gaspari
authors.forename: Aage
authors.initials: A
authors.lastname: Haugen
authors.forename: Ari
authors.initials: A
authors.lastname: Hirvonen
authors.forename: Kirsti
authors.initials: K
authors.lastname: Husgafvel-Pursiainen
authors.forename: Magnus
authors.initials: M
authors.lastname: Ingelman-Sundberg
authors.forename: Ivan
authors.initials: I
authors.lastname: Kalina
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kihara
authors.forename: Pierre
authors.initials: P
authors.lastname: Kremers
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: London
authors.forename: Valle
authors.initials: V
authors.lastname: Nazar-Stewart
authors.forename: Masako
authors.initials: M
authors.lastname: Onon-Kihara
authors.forename: Agneta
authors.initials: A
authors.lastname: Rannug
authors.forename: Marjorie
authors.initials: M
authors.lastname: Romkes
authors.forename: David
authors.initials: D
authors.lastname: Ryberg
authors.forename: Janeric
authors.initials: J
authors.lastname: Seidegard
authors.forename: Peter
authors.initials: P
authors.lastname: Shields
authors.forename: Richard C
authors.initials: RC
authors.lastname: Strange
authors.forename: Isabelle
authors.initials: I
authors.lastname: Stücker
authors.forename: Jordi
authors.initials: J
authors.lastname: To-Figueras
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.forename: Emanuela
authors.initials: E
authors.lastname: Taioli
mesh_terms: D016022:Case-Control Studies; D003043:Cocarcinogenesis; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000208:ethnology / Q000209:etiology* / Q000235:genetics; D011110:Polymorphism, Genetic; D012907:Smoking / Q000009:adverse effects*
chemical_list: D005982:Glutathione Transferase