Null genotypes of GSTM1 and GSTT1 contribute to hepatocellular carcinoma risk: evidence from an updated meta-analysis.
OBJECTIVE
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.
Wang
Bin
B
The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China.
Huang
Gang
G
Wang
Dan
D
Li
Aijun
A
Xu
Zhipeng
Z
Dong
Ran
R
Zhang
Deqiang
D
Zhou
Weiping
W
D044466:Asian People / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000209:etiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors
D005982:Glutathione Transferase; C413545:glutathione S-transferase T1