Meta- and pooled analyses of the effects of glutathione S-transferase M1 polymorphisms and smoking on lung cancer risk.
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.
Benhamou
Simone
S
INSERM U521, EMI 00-06, Evry, France. benhamou@evry.inserm.fr
Lee
Won Jin
WJ
Alexandrie
Anna-Karin
AK
Boffetta
Paolo
P
Bouchardy
Christine
C
Butkiewicz
Dorota
D
Brockmöller
Jurgen
J
Clapper
Margie L
ML
Daly
Ann
A
Dolzan
Vita
V
Ford
Jean
J
Gaspari
Laura
L
Haugen
Aage
A
Hirvonen
Ari
A
Husgafvel-Pursiainen
Kirsti
K
Ingelman-Sundberg
Magnus
M
Kalina
Ivan
I
Kihara
Masahiro
M
Kremers
Pierre
P
Le Marchand
Loïc
L
London
Stephanie J
SJ
Nazar-Stewart
Valle
V
Onon-Kihara
Masako
M
Rannug
Agneta
A
Romkes
Marjorie
M
Ryberg
David
D
Seidegard
Janeric
J
Shields
Peter
P
Strange
Richard C
RC
Stücker
Isabelle
I
To-Figueras
Jordi
J
Brennan
Paul
P
Taioli
Emanuela
E
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*
D005982:Glutathione Transferase