GSTM1 and GSTT1 null genotype increase the risk of hepatocellular carcinoma: evidence based on 46 studies

Abstract

Background It is well known that hepatocellular carcinoma (HCC) has been one of the most life-threatening diseases all over the world. Plenty of internal and extrinsic factors have been proven to be related to HCC, such as gene mutation, viral hepatitis, and Nitrosamines. Though previous studies demonstrated that glutathione S -transferase (GST) genotypes are associated with HCC, the conclusions are inconsistent. Therefore, we carried on a renewed meta-analysis to expound the connection between the null GSTM1, GSTT1 polymorphisms and the risk of HCC. Methods We searched PubMed, Web of Science, Embase, and CNKI databases to select qualified researches which satisfied the inclusion criteria up to July 31, 2018. Finally, we selected 41 articles with 6124 cases and 9781 controls in this meta-analysis. We use ORs and 95% confidence interval (CI) to evaluate the correlation intension between the GSTM1 and GSTT1 null genes and the risk of HCC. All the statistical processes were executed by Stata (version 12.0). Results The pooled analysis showed that both GSTM1 null genotypes (OR = 1.37, 95% CI = 1.18–1.59) and GSTT1 null genotypes (OR = 1.43, 95% CI = 1.23–1.66) increased the risk of HCC. And GSTM1–GSTT1 dual-null genotypes also increased the risk of HCC (OR = 1.58, 95% CI = 1.22–2.05). In the subgroup analysis, we obtained significant results among Asians when stratified by race, and the results are GSTM1 null OR = 1.44, 95% CI = (1.22–1.71), GSTT1 null OR = 1.48, 95% CI = (1.25–1.77), GSTM1–GSTT1 null OR = 1.58, 95% CI = (1.19–2.09), while we didn’t obtain significant results among Caucasians or Africans. Stratified analyses on the type of control indicated a higher risk of HCC associated with GSTM1, GSTT1 single null genotypes and GSTM1–GSTT1 dual-null genotypes in healthy people. No evidence of significant connection was discovered in chronic liver disease (CLD) except in GSTT1 single null. Conclusions Our study indicated that an individual who carries the GSTM1, GSTT1 single null genotypes and GSTT1–GSTM1 dual-null genotypes is more likely to develop HCC. Electronic supplementary material The online version of this article (10.1186/s12935-019-0792-3) contains supplementary material, which is available to authorized users.

Identification of Methylation-Regulated Differentially Expressed Genes and Related Pathways in Hepatocellular Carcinoma: A Study Based on TCGA Database and Bioinformatics Analysis

“…Feng et al (32) have indicated that TGFB3 can function as a modulator to promote the metastatic phenotype of nonmetastatic HCC cells induced by TGFB1. GSTM1 polymorphisms have been identified as biomarkers of HCC development and risk in different regions (33)(34)(35)(36)(37).…”

Research Article Evidence of association of glutathione-S-transferase <i>GSTT1</i> and <i>GSTM1</i> null genotypes with susceptibility to oral cancer based on meta-analysis

“…A recent meta-analysis, including 46 studies, concluded that GSTT1 and GSTM1 null genotypes are associated with an increased risk of developing hepatocellular carcinoma (Li et al, 2019). Another study showed the association of GSTT1 null genotype with a greater risk of developing osteosarcoma (Moghimi et al, 2019).…”

Polymorphism of Glutathione S-transferase Genes and the Risk of Toxic Liver Damage in Petrochemical Workers

“…The presence of two null alleles of the GSTM1 gene leads to the absence of the protein product of this gene, which contributes to the development of oxidative stress, causes an increase in the level of DNA adducts and can provoke the development of various liver pathologies. 11,12 A number of research findings show its important prognostic significance in the development of occupational diseases. 13,14 In contrast to these results, our study showed that there was no significant difference in the distribution of the GSTM1 gene genotypes among workers depending on the presence or absence of occupational pathology.…”