Association of GST genetic polymorphisms with the susceptibility to hepatocellular carcinoma (HCC) in Chinese population evaluated by an updated systematic meta-analysis

PLoS One. 2013;8(2):e57043. doi: 10.1371/journal.pone.0057043. Epub 2013 Feb 20.

Abstract

Background: Due to the possible involvement of Glutathione S-transferase Mu-1 (GSTM1) and Glutathione S-transferase theta-1 (GSTT1) in the detoxification of environmental carcinogens, environmental toxins, and oxidative stress products, genetic polymorphisms of these two genes may play important roles in the susceptibility of human being to hepatocellular carcinoma. However, the existing research results are not conclusive.

Methods: A systematic literature search using databases (PubMed, Scopus, Embase, Chinese Biomedical Database, Chinese National Knowledge Infrastructure, Wanfang Data, etc.) for the eligible studies meeting the inclusion criteria including case-control studies or cohort studies is evaluated using an updated systematic meta-analysis.

Results: Significant increase in the risk of HCC in the Chinese population is found in GSTM1 null genotype (OR = 1.47, 95% CI: 1.21 to 1.79, P<0.001) and GSTT1 null genotype (OR = 1.38, 95% CI: 1.14 to 1.65, P<0.001). Analysis using the random-effects model found an increased risk of HCC in GSTM1-GSTT1 dual null population (OR = 1.79, 95% CI: 1.26 to 2.53, P<0.001). In addition, subgroup analyses showed a significant increase in the association of GST genetic polymorphisms (GSTM1, GSTT1, and GSTM1-GSTT1) with HCC in southeast and central China mainland. However, available data collected by this study fail to show an association between GST genetic polymorphisms and HCC in people from the Taiwan region (for GSTM1: OR = 0.78, 95% CI: 0.60 to 1.01, P = 0.06; for GSTT1: OR = 0.94, 95% CI: 0.78 to 1.14, P = 0.546; for GSTM1-GSTT1: OR = 1.04, 95% CI: 0.81 to 1.32, P = 0.77). Sensitivity analysis and publication bias diagnostics confirmed the reliability and stability of this meta-analysis.

Conclusions: Our results indicate that both GSTM1 and GSTT1 null genotypes are associated with an increased HCC risk in Chinese population. Peoples with dual null genotypes of GSTM1-GSTT1 are more susceptible to developing HCC. In conclusion, GST genetic polymorphisms play vital roles in the development of HCC in the Chinese population.

Publication types

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

MeSH terms

  • Asian People / genetics*
  • Carcinoma, Hepatocellular / genetics*
  • China
  • Genetic Predisposition to Disease*
  • Genotype
  • Glutathione Transferase / genetics*
  • Humans
  • Liver Neoplasms / genetics*
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • Publication Bias

Substances

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

Grants and funding

Funding provided by grant number: 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). This work was partly supported by 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.