Association between glutathione S-transferase p1 polymorphisms and lung cancer risk in Caucasians: a case-control study

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• 作者：Wang ; Yunfei ; Spitz ; Margaret R. ; Schabath ; Matthew B. ; Ali-Osman ; Francis ; Mata ; Hilario ; et. al.
• 关键词：Lung cancer ; Genetic susceptibility ; Molecular epidemiology ; Single nucleotide polymorphism
• 刊名：Lung Cancer
• 出版年：2003
• 出版时间：April, 2003
• 年：2003
• 卷：40
• 期：1
• 页码：25-32
• 全文大小：130 K

文摘

Glutathione transferases (GSTs), a multiple gene family of phase II enzymes, catalyze detoxifying endogenous reactions with glutathione and protect cellular macromolecules from damage caused by cytotoxic and carcinogenic agents. Glutathione S-transferase p1 (GSTP1), the most abundant GST isoform in the lung, metabolizes numerous carcinogenic compounds including benzo[a]pyrene, a tobacco carcinogen. Previous studies suggest that genetic polymorphisms of GSTP1 exon 5 (Ile105Val) and exon 6 (Ala114Val) have functional effects on the GST gene product resulting in reduced enzyme activity. Individuals with reduced GST enzymatic activity may be at a greater risk for cancer due to decreased detoxification of carcinogenic and mutagenic compounds. Utilizing a hospital-based case-control study, we investigated the association between GSTP1 polymorphisms at exons 5 and 6 with lung cancer risk. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was used to successfully genotype the GSTP1 exons 5 and 6 polymorphism in 582 Caucasian lung cancer cases and 600 frequency matched Caucasian controls. There was no association between the exon 5 variant genotypes (A/G+G/G) and overall lung cancer risk (OR=1.09; 95 % CI 0.82–1.45) nor when stratified by age, gender, and smoking status. However, the exon 6 variant genotypes (C/T+T/T) were associated with a statistically significant elevated lung cancer risk (OR=1.40; 95 % CI 1.06–1.92). Additionally, there was an increase in lung cancer risk for the exon 6 variant genotypes in younger individuals (<62 years) (OR=1.63; 95 % C.I. 1.07–2.49) but no effect in older individuals (OR=1.14; 95 % CI 0.72–1.81). A statistically significant increased risk of lung cancer was also observed for the exon 6 variant genotypes among men (OR=2.17; 95 % CI 1.41–3.33), but not among women (OR=0.80; 95 % CI 0.51–1.28). Among ever smokers, the exon 6 variant genotypes were associated with an elevated lung cancer risk (OR=1.58; 95 % CI 1.14–2.19), which was not evident for never smokers (OR=0.53; 95 % CI 0.21–1.33). These data demonstrate that the GSTP1 exon 6 polymorphism, but not the exon 5 polymorphism, is associated with lung cancer risk that is especially evident in men, younger individuals, and ever smokers.