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Quantitative assessment of the effect of glutathione S-transferase genes GSTM1 and GSTT1 on hepatocellular carcinoma risk

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Tumor Biology

Abstract

Hepatocellular carcinoma (HCC) is one of the most serious health problems worldwide. As in many other diseases, environment and genetic factors are believed to be involved in the pathogenesis of HCC. Numerous epidemiologic investigations including case–control and cohort studies have suggested the association of glutathione S-transferase (GST) genetic polymorphisms and HCC risk. However, some studies have produced conflicting results. Therefore, we performed an updated meta-analysis to clarify this inconsistency and to establish a comprehensive picture of the association of the polymorphisms of GSTM1 and GSTT1 with HCC susceptibility. We searched PubMed, Embase, ISI Web of Science, and CNKI databases to identify eligible studies meeting the inclusion criteria up to August 30, 2013. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the strength of association. Finally, there were a total of 33 studies with 4,232 cases and 6,601 controls included in this meta-analysis. In the pooled analysis, significantly increased HCC risks were found for null genotype of GSTM1 (OR = 1.31, 95 % CI = 1.07–1.61, P = 0.010, P heterogeneity < 10−5) and GSTT1 (OR = 1.47, 95 % CI = 1.25–1.74, P < 10−5, P heterogeneity < 10−5). Potential sources of heterogeneity were explored by subgroup analysis based on ethnicity, sample size, and source of control. Significant results were found among East Asians and Indians when stratified by ethnicity, while no evidence of significant associations was observed among Caucasian and African populations. In the gene–gene interaction analysis, a statistically significant increased risk for HCC was detected for individuals with combined deletion mutations in both genes compared to those with wild genotypes (OR = 1.88, 95 % CI = 1.41–2.50, P < 10−4, P heterogeneity = 0.004). The present meta-analysis demonstrated that the GSTM1 and GSTT1 null genotype may be associated with an increased risk of HCC and that individuals having the combination of both defective GST genotypes may be more susceptible to developing HCC.

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Acknowledgments

We thank all the participants. This work was supported by Rising Star Project in Science and Technology of Shanghai (13QH1401000) and Shanghai Health Bureau scientific research found projects (no. 2008Y082).

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  1. Department of Liver Surgery, Zhongshan Hospital, Liver Cancer Institute, Fudan University, 180 Feng-Lin Road, Shanghai, 200032, China

    Ying-Hao Shen, Si Chen, Yuan-Fei Peng, Ying-Hong Shi, Xiao-Wu Huang, Guo-Huan Yang, Zhen-Bin Ding, Yong Yi, Jian Zhou, Shuang-Jian Qiu, Jia Fan & Ning Ren

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  1. Ying-Hao Shen
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  2. Si Chen
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Correspondence to Jia Fan or Ning Ren.

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Ying-Hao Shen and Si Chen contributed equally to this work.

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Shen, YH., Chen, S., Peng, YF. et al. Quantitative assessment of the effect of glutathione S-transferase genes GSTM1 and GSTT1 on hepatocellular carcinoma risk. Tumor Biol. 35, 4007–4015 (2014). https://doi.org/10.1007/s13277-013-1524-2

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