American Journal of Epidemiology Advance Access originally published online on December 7, 2007
American Journal of Epidemiology 2008 167(4):377-389; doi:10.1093/aje/kwm315
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Genetic Variants of Glutathione S-Transferase as Possible Risk Factors for Hepatocellular Carcinoma: A HuGE Systematic Review and Meta-Analysis
1 The Sections of Gastroenterology and Health Services Research, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX
2 MD Anderson Cancer Medical Center, Houston, TX
Correspondence to Dr. Hashem El-Serag, Michael E. DeBakey Veterans Affairs Medical Center, Room 152, 2002 Holcombe Boulevard, Houston, TX 77030 (e-mail: hasheme{at}bcm.tmc.edu).
Received for publication March 8, 2007. Accepted for publication September 24, 2007.
The authors performed a systematic review and meta-analysis to determine the effect of polymorphisms in genes encoding glutathione S-transferases (GSTs), phase II isoenzymes involved in cellular detoxification, on risk of hepatocellular carcinoma (HCC). Fifteen eligible studies were identified: 14 evaluated GSTM1; 13, GSTT1; three, GSTP1; and one each evaluated GSTM2, GSTM3, GSTA1, GSTA4, GSTO1, and GSTO2, respectively. All were case-control studies performed in populations with high (Asian, African) and medium (European) HCC incidence rates. Random-effects meta-analyses suggested a small excess risk of HCC with GSTT1 null (odds ratio (OR) = 1.19, 95% confidence interval (CI): 0.99, 1.44) and possibly GSTM1 null (OR = 1.16, 95% CI: 0.89, 1.53) genotypes. Cumulative meta-analyses demonstrated that both pooled estimators generally trended toward a small excess risk with publication of more recent studies. Results for GSTP1 A313G suggested no excess risk (OR = 0.75, 95% CI: 0.50, 1.15). A number of potentially interesting gene-gene and gene-environment interactions were reported, but these were too few and inconsistent to allow meta-analysis. The overall results suggest that there may be a small excess risk of HCC in individuals with GSTT1 null and possibly also with GSTM1 null genotypes. However, given the relatively limited total number of subjects examined and observed between-study heterogeneity, chance could not be excluded.
carcinoma, hepatocellular; epidemiology; genetics; glutathione S-transferase pi; glutathione transferase; humans; liver neoplasms; meta-analysis
Abbreviations: CI, confidence interval; GST, glutathione S-transferase; HCC, hepatocellular carcinoma; OR, odds ratio
Editor's note: This paper is also available on the website of the Human Genome Epidemiology Network (http://www.cdc.gov/genomics/hugenet/).