title: CYP1A1, GSTM1 and GSTT1 polymorphisms and lung cancer: a pooled analysis of gene-gene interactions.
abstract: Gene-environment interactions have been extensively studied in lung cancer. It is likely that several genetic polymorphisms cooperate in increasing the individual risk. Therefore, the study of gene-gene interactions might be important to identify high-susceptibility subgroups. GSEC is an initiative aimed at collecting available data sets on metabolic polymorphisms and the risks of cancer at several sites and performing pooled analyses of the original data. Authors of published papers have provided original data sets. The present paper refers to gene-gene interactions in lung cancer and considers three polymorphisms in three metabolic genes: CYP1A1, GSTM1 and GSTT1. The present analyses compare the gene gene interactions of the CYP1A1*2A, GSTM1 and GSTT1 polymorphisms from studies on lung cancer conducted in Europe and the USA between 1991 and 2000. Only Caucasians have been included. The data set includes 1466 cases and 1488 controls. The only clear-cut association was found with CYP1A1*2A. This association remained unchanged after stratification by polymorphisms in other genes (with an odds ratio [OR] of approximately 2.5), except when interaction with GSTM1 was considered. When the OR for CYP1A1*2A was stratified according to the GSTM1 genotype, the OR was increased only among the subjects who had the null (homozygous deletion) GSTM1 genotype (OR = 2.8, 95% CI = 0.9-8.4). The odds ratio for the interactive term (CYP1A1*2A by GSTM1) in logistic regression was 2.7 (95% CI = 0.5-15.3). An association between lung cancer and the homozygous CYP1A1*2A genotype is confirmed. An apparent and biologically plausible interaction is suggested between this genotype and GSTM1.
authors.affiliation: Imperial College London, London, UK.
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Veglia
authors.forename: Sisko
authors.initials: S
authors.lastname: Anttila
authors.forename: Simone
authors.initials: S
authors.lastname: Benhamou
authors.forename: Margie L
authors.initials: ML
authors.lastname: Clapper
authors.forename: Vita
authors.initials: V
authors.lastname: Dolzan
authors.forename: David
authors.initials: D
authors.lastname: Ryberg
authors.forename: Ari
authors.initials: A
authors.lastname: Hirvonen
authors.forename: Pierre
authors.initials: P
authors.lastname: Kremers
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Roberta
authors.initials: R
authors.lastname: Pastorelli
authors.forename: Agneta
authors.initials: A
authors.lastname: Rannug
authors.forename: Marjorie
authors.initials: M
authors.lastname: Romkes
authors.forename: Bernadette
authors.initials: B
authors.lastname: Schoket
authors.forename: Richard C
authors.initials: RC
authors.lastname: Strange
authors.forename: Seymour
authors.initials: S
authors.lastname: Garte
authors.forename: Emanuela
authors.initials: E
authors.lastname: Taioli
mesh_terms: D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D019992:Databases as Topic; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D013997:Time Factors
chemical_list: D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1