Five Glutathione S-Transferase Gene Variants in 23,452 Cases of Lung Cancer and 30,397 Controls: Meta-Analysis of 130 Studies

Abstract

BackgroundGlutathione S-transferases (GSTs) are known to abolish or reduce the activities of intracellular enzymes that help detoxify environmental carcinogens, such as those found in tobacco smoke. It has been suggested that polymorphisms in the GST genes are risk factors for lung cancer, but a large number of studies have reported apparently conflicting results. Methods and FindingsLiterature-based meta-analysis was supplemented by tabular data from investigators of all relevant studies of five GST polymorphisms ( GSTM1 null, GSTT1 null, I105V, and A114V polymorphisms in the GSTP1 genes, and GSTM3 intron 6 polymorphism) available before August, 2005, with investigation of potential sources of heterogeneity. Included in the present meta-analysis were 130 studies, involving a total of 23,452 lung cancer cases and 30,397 controls. In a combined analysis, the relative risks for lung cancer of the GSTM1 null and GSTT1 null polymorphisms were 1.18 (95% confidence interval [CI]: 1.14–1.23) and 1.09 (95% CI: 1.02–1.16), respectively, but in the larger studies they were only 1.04 (95% CI: 0.95–1.14) and 0.99 (95% CI: 0.86–1.11), respectively. In addition to size of study, ethnic background was a significant source of heterogeneity among studies of the GSTM1 null genotype, with possibly weaker associations in studies of individuals of European continental ancestry. Combined analyses of studies of the 105V, 114V, and GSTM3*B variants showed no significant overall associations with lung cancer, yielding per-allele relative risks of 1.04 (95% CI: 0.99–1.09), 1.15 (95% CI: 0.95–1.39), and 1.05 (95% CI: 0.89–1.23), respectively. ConclusionsThe risk of lung cancer is not strongly associated with the I105V and A114V polymorphisms in the GSTP1 gene or with GSTM3 intron 6 polymorphism. Given the non-significant associations in the larger studies, the relevance of the weakly positive overall associations with the GSTM1 null and the GSTT1 null polymorphisms is uncertain. As lung cancer has important environmental causes, understanding any genetic contribution to it in general populations will require the conduct of particularly large and comprehensive studies.

Glutathione S-transferase mu, omega, pi, and theta class variants and smoking in Parkinson's disease

“…Each of the GST classes selected has previously been shown to interact with cigarette smoking in the context of cancer [11,12,26,31], and metabolic substrates for each GST class have been proposed or identified among the myriad components of cigarette smoke [11,28,7]. To the best of our knowledge, this is the first study to examine the interaction of the GST omega class and smoking in PD.…”

GST genotypes and lung cancer susceptibility in Asian populations with indoor air pollution exposures: A meta-analysis

“…In the most recent meta-analysis of 119 studies, almost all of which were carried out in populations where tobacco use is likely to be the primary cause of lung cancer, the GSTM1 null genotype was associated with a significantly increased lung cancer risk (OR, 1.18; 95% CI, 1.14-1.23) [32]. However, there was strong evidence of publication bias from positive findings in smaller studies (Begg's test p < 0.0001).…”

“…The association between lung cancer and the GSTM1 deletion, GSTT1 deletion, and GSTP1 Ile105Val polymorphisms have been studied and reviewed in meta-analyses and a pooled analysis, with most work focusing on the GSTM1 null genotype [32][33][34][35]. After consideration of potential publication bias, there is little evidence that the GSTM1 null genotype is associated with risk of lung cancer, either among ever-smokers or never-smokers [32;33].…”

Role of Household Exposure, Dietary Habits and Glutathione S-Transferases M1, T1 Polymorphisms in Susceptibility to Lung Cancer among Women in Mizoram India

“…Functional genetic polymorphisms of Phase II metabolic pathways genes GST also may account for differences in metabolic inactivation of dietary or other environmental carcinogens (Ye et al, 2006). Among these, the best known are deletion of GST mu 1 (GSTM1) or GST theta 1 (GSTT1) genes (null variant), which result in no functional activity (Kelsey et al, 1997).…”