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

Abstract

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, I2 = 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, I2 = 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, I2 = 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, I2 = 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, I2 = 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, I2 = 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.