Abstract
BackgroundDue 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.MethodsA 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.ResultsSignificant 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.ConclusionsOur 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.
Highlights
Due to a high mortality, hepatocellular carcinoma (HCC) is one of the most serious health problems worldwide [1,2], which is consisted of approximately 80% of all primary tumors of liver [3]
Literature and Research Strategy A computerized literature search was carried out in Embase, PubMed, Scopus, Chinese Biomedical Database (CBM), CochraneLibrary, Chinese National Knowledge Infrastructure (CNKI), and Wanfang Data to collect articles with case-control or cohort studies related to the association of Glutathione S-transferase Mu-1 (GSTM1) and/or Glutathione S-transferase theta-1 (GSTT1) polymorphisms with the susceptibility of HCC in China
Study Selection and Study Characteristics We identified a total of 27 articles reporting the relationship between Glutathione S-transferases (GSTs) genetic polymorphisms and HCC risk by both Chinese and English database [24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50] (Figure 1)
Summary
Due to a high mortality, hepatocellular carcinoma (HCC) is one of the most serious health problems worldwide [1,2], which is consisted of approximately 80% of all primary tumors of liver [3]. Incidence rate of HCC has been increasing for several years while overall cancer incidence rate has been decreasing in recent years [4,5]. In Asia, people are at higher risk of developing HCC because of chronic infection with hepatitis B virus (HBV) [12,13]. In Europe, hepatitis C virus (HCV) and cirrhosis, but alcohol and tobacco smoking are clearly able to accelerate HCC development [2]. Due to its substantial morbidity and mortality, HCC has been a hot research topic in China in recent years.
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