Null genotypes of GSTM1 and GSTT1 contribute to hepatocellular carcinoma risk: evidence from an updated meta-analysis

Background & aims: Studies investigating the associations between glutathione S-transferase (GST) genetic polymorphisms and hepatocellular carcinoma (HCC) risk have reported controversial results. Thus, a meta-analysis was performed to clarify the effects of GSTM1 and GSTT1 polymorphisms on HCC risk.

Methods: We identified 132 relevant records through a literature search up to November 22, 2009, and 24 individual case-control studies from 23 publications were finally included, involving a total of 3349 HCC cases and 5609 controls. Subgroup analyses were performed by ethnicity, or by area according to the incidence rate and hepatitis virus status.

Results: Analyses of total relevant studies showed an increased HCC risk was significantly associated with null genotypes of GSTM1 (OR=1.26, 95% CI 1.03-1.54, p(OR)=0.027) and GSTT1 (OR=1.28, 95% CI 1.09-1.51, p(OR)=0.002). In addition, the GSTM1-GSTT1 interaction analysis showed that the dual null genotype of GSTM1/GSTT1 was significantly associated with increased HCC risk (OR=1.89, 95% CI 1.38-2.60, p(OR)<0.001). Subgroup analyses showed that the associations above were still statistically significant in Asians (p(GSTM1)=0.017, p(GSTT1)=0.001, p(Dual null genotype)<0.001), high-rate areas (p(GSTM1)=0.012, p(GSTT1)=0.006, p(Dual null genotype)<0.001), and HBV-dominant areas (p(GSTM1)=0.003, p(GSTT 1)=0.003, p(Dual null genotype)<0.001).

Conclusions: This meta-analysis suggests null genotypes of GSTM1 and GSTT1 are both associated with increased HCC risk in Asians, and individuals with the dual null genotype of GSTM1/GSTT1 are particularly susceptible to developing HCC.