Individual and combined effects of GSTM1, GSTT1, and GSTP1 polymorphisms on lung cancer risk A meta-analysis and re-analysis of systematic meta-analyses

Thirty-five previous meta-analyses have been reported on the individual glutathione S-transferase M1 (GSTM1) present/null, glutathione S-transferase T1 (GSTT1) present/null, and glutathione S-transferase P1 (GSTP1) IIe105Val polymorphisms with lung cancer (LC) risk. However, they did not appraise the credibility and explore the combined effects between the 3 genes and LC risk. We performed a meta-analysis and re-analysis of systematic previous meta-analyses to solve the above problems. Meta-analyses of Observational Studies in Epidemiology guidelines were used. Moreover, we employed false-positive report probability (FPRP), Bayesian false discovery probability (BFDP), and the Venice criteria to verify the credibility of current and previous meta-analyses. Significantly increased LC risk was considered as highly credible or positive for GSTM1 null genotype in Japanese (odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.17-1.44, I-2 = 0.0%, statistical power = 0.997, FPRP = 0.008, BFDP = 0.037, and Venice criteria: AAB), for GSTT1 null genotype in Asians (OR = 1.23, 95% CI = 1.12-1.36, I-2 = 49.1%, statistical power = 1.000, FPRP = 0.051, BFDP = 0.771, and Venice criteria: ABB), especially Chinese populations (OR = 1.31, 95% CI = 1.16-1.49, I-2 = 48.9%, Statistical power = 0.980, FPRP = 0.039, BFDP = 0.673, and Venice criteria: ABB), and for GSTP1 IIe105Val polymorphism in Asians (Val vs IIe: OR = 1.28, 95% CI = 1.17-1.42, I-2 = 30.3%, statistical power = 0.999, FPRP = 0.003, BFDP = 0.183, and Venice criteria: ABB). Significantly increased lung adenocarcinoma (AC) risk was also considered as highly credible or positive in Asians for the GSTM1 (OR = 1.35, 95% CI = 1.22-1.48, I-2 = 25.5%, statistical power = 0.988, FPRP < 0.001, BFDP < 0.001, and Venice criteria: ABB) and GSTT1 (OR = 1.36, 95% CI = 1.17-1.58, I-2 = 30.2%, statistical power = 0.900, FPRP = 0.061, BFDP = 0.727, and Venice criteria: ABB) null genotype. This study indicates that GSTM1 null genotype is associated with increased LC risk in Japanese and lung AC risk in Asians; GSTT1 null genotype is associated with increased LC risk in Chinese, and GSTP1 IIe105Val polymorphism is associated with increased LC risk in Asians.

Automated summary

This study found that the GSTM1 null genotype is associated with an increased risk of lung cancer in Japanese individuals, while the GSTT1 and GSTP1 IIe105Val polymorphisms are significantly related to lung cancer risk in Asians.