The associations between two vital GSTs genetic polymorphisms and lung cancer risk in the Chinese population: evidence from 71 studies

PLoS One. 2014 Jul 18;9(7):e102372. doi: 10.1371/journal.pone.0102372. eCollection 2014.

Abstract

Background: The genetic polymorphisms of glutathione S-transferase (GSTs) have been suspected to be related to the development of lung cancer while the current results are conflicting, especially in the Chinese population.

Methods: Data on genetic polymorphisms of glutathione S-transferase Mu 1 (GSTM1) from 68 studies, glutathione S-transferase theta 1 (GSTT1) from 17 studies and GSTM1-GSTT1 from 8 studies in the Chinese population were reanalyzed on their association with lung cancer risk. Odds ratios (OR) were pooled using forest plots. 9 subgroups were all or partly performed in the subgroup analyses. The Galbraith plot was used to identify the heterogeneous records. Potential publication biases were detected by Begg's and Egger's tests.

Results: 71 eligible studies were identified after screening of 1608 articles. The increased association between two vital GSTs genetic polymorphisms and lung cancer risk was detected by random-effects model based on a comparable heterogeneity. Subgroup analysis showed a significant relationship between squamous carcinoma (SC), adenocarcinoma (AC) or small cell lung carcinoma (SCLC) and GSTM1 null genotype, as well as SC or AC and GSTT1 null genotype. Additionally, smokers with GSTM1 null genotype had a higher lung cancer risk than non-smokers. Our cumulative meta-analysis demonstrated a stable and reliable result of the relationship between GSTM1 null genotype and lung cancer risk. After the possible heterogeneous articles were omitted, the adjusted risk of GSTs and lung cancer susceptibility increased (fixed-effects model: ORGSTM1 = 1.23, 95% CI: 1.19 to 1.27, P<0.001; ORGSTT1 = 1.18, 95% CI: 1.10 to 1.26, P<0.001; ORGSTM1-GSTT1 = 1.33, 95% CI: 1.10 to 1.61, P = 0.004).

Conclusions: An increased risk of lung cancer with GSTM1 and GSTT1 null genotype, especially with dual null genotype, was found in the Chinese population. In addition, special histopathological classification of lung cancers and a wide range of gene-environment and gene-gene interaction analysis should be taken into consideration in future studies.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Glutathione Transferase / genetics*
  • Humans
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / genetics*
  • Polymorphism, Genetic*

Substances

  • glutathione S-transferase T1
  • Glutathione Transferase
  • glutathione S-transferase M1

Grants and funding

This work was supported by the National Nature Science Foundation of China (Grant No. 81273111), the Foundations of Innovative Research Team of Educational Commission of Zhejiang Province (T200907), the Nature Science Foundation of Ningbo city (Grant No. 2012A610185), the Ningbo Scientific Projects (2012C5019 and SZX11073), the Scientific Innovation Team Project of Ningbo (No. 2011B82014), Innovative Research Team of Ningbo (2009B21002), and K.C. Wong Magna Fund in Ningbo University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.