Meta- and pooled analyses of the effects of glutathione S-transferase M1 polymorphisms and smoking on lung cancer risk

Abstract

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.

Role ofCYP2D6, CYP1A1, CYP2E1, GSTT1, andGSTM1 genes in the susceptibility to acute leukemias

“…There was a significant increase in *1/*5 genotype in both the AML (OR ¼ 3.9) and ALL (OR ¼ 3.6) groups. CYP2E1 variants have been found to be associated with the susceptibility to several cancers such as colorectal [39], lung [40,41], stomach [42], lymphoma [23], and acute lymphoblastic leukemia [36,43]. CYP2E1 gene RsaI polymorphism in the 5 0 flanking (promoter) region affects its transcriptional activity [44].…”

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

“…Restriction to the five studies with greater than 500 cases yielded no association with the GSTM1 null genotype (OR = 1.04; 95% CI, 0.95-1.14). A pooled analysis of 21 studies found similar risks for ever-smokers (OR, 1.1; 95% CI, 1.0 -1.2) and never-smokers (OR, 1.1; 95% CI, 0.8 -1.4) [33]. In sub-analyses for studies carried out in Asia, there was a non-significant increase in risk for ever-smokers (OR, 1.2; 95% CI, 0.9 -1.7) and a non-significant decrease in risk for never-smokers (OR, 0.7; 95% CI, 0.4 -1.4).…”

“…In sub-analyses for studies carried out in Asia, there was a non-significant increase in risk for ever-smokers (OR, 1.2; 95% CI, 0.9 -1.7) and a non-significant decrease in risk for never-smokers (OR, 0.7; 95% CI, 0.4 -1.4). However, these estimates were based on a relatively small number of study subjects [33]. Overall, the weight of evidence suggests that the GSTM1 null genotype is associated with at most a small risk of lung cancer.…”

“…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].…”

The genetics of cardiovascular disease

“…Previous genome scans were limited by the 25 in SHRSP and chromosome 2 congenic strains [34,35], GSTM genes were subject to association 1 studies in humans [39][40][41] due to the fundamental role of the oxidative stress pathway in 2 cardiovascular pathophysiology [42,43]. While there is agreement on the involvement of genetic 3 variants of GSTMs in the development of cancer [44,45], studies on the role of GSTMs in 4 cardiovascular diseases are less consistent [40,41]. This inconsistency suggests the necessity for 5 setting quality criteria for genetic association studies.…”