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CYP1A1, GSTM1 and GSTT1 polymoprhisms and lung cancer: a pooled analysis of gene-gene interations
Vineis, Paolo ...
Gene-environment interactions have been extensively studied in lung caacer. Itis 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. GSEG is an initiative aimed at collecting available data sets un metabolic polymorphisms and the risks of cancer at several sites aad 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 conductedin 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 associatian remained unchanged after stratification by polymorphisms in other genes (with an odds ratin šORđ of approximately 2.5), except when interaction with GSTM1 was considered. When the OR for CYP1A1*2A was stratified according ta the GSTM1 genotype, the OR was inereased only among the subjects who had the null (homoxygous 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 was2.7 (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.
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