Abstract
BackgroundHepatocarcinogenesis is a complex process that may be influenced by many factors, including polymorphism in microsomal epoxide hydrolase (mEH). Previous work suggests an association between the Tyr113His and His139Arg mEH polymorphisms and susceptibility to hepatocellular carcinoma (HCC), but the results have been inconsistent.MethodsPubMed, EMBASE, Google Scholar and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. A meta-analysis was performed to examine the association between Tyr113His and His139Arg mEH polymorphism and susceptibility to HCC. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.ResultsEleven studies were included in the meta-analysis, involving 1,696 HCC cases and 3,600 controls. The 113His- mEH allele was significantly associated with increased risk of HCC based on allelic contrast (OR = 1.35, 95% CI = 1.04–1.75, p = 0.02), homozygote comparison (OR = 1.65, 95% CI = 1.07–2.54, p = 0.02) and a recessive genetic model (OR = 1.54, 95% CI = 1.21–1.96, p<0.001), while individuals carrying the Arg139Arg mEH genotype had no association with increased or decreased risk of HCC.ConclusionThe 113His- allele polymorphism in mEH may be a risk factor for hepatocarcinogenesis, while the mEH 139Arg- allele may not be a risk or protective factor. There is substantial evidence that mEH polymorphisms interact synergistically with other genes and the environment to modulate risk of HCC. Further large and well-designed studies are needed to confirm these conclusions.
Highlights
As the most frequent primary cancer of the liver, hepatocellular carcinoma (HCC) is a significant cause of cancer morbidity and mortality worldwide, and treatment options are limited
Inclusion Criteria A study was included in the meta-analysis if it satisfied the following criteria: (a) it assessed the association between HCC and the Tyr113His and His139Arg microsomal epoxide hydrolase (mEH) gene polymorphisms, (b) it used a case-control design, and (c) it provided sufficient published data for estimating an odds ratio (OR) with a 95% confidence interval
Statistical Methods The unadjusted OR with 95% confidence intervals (95% CIs) was used to assess the strength of the association between the Tyr113His and His139Arg mEH polymorphisms and HCC risk based on the genotype frequencies in cases and controls
Summary
As the most frequent primary cancer of the liver, hepatocellular carcinoma (HCC) is a significant cause of cancer morbidity and mortality worldwide, and treatment options are limited. The estimated incidence of new HCC cases each year is more than 0.5 million [1]. HCC is strongly associated with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, alcohol consumption, and aflatoxin B1 (AFB) contamination of foodstuffs, among other factors [3,4]. AFB together with chronic HBV infection contributes to the high incidence of HCC. Not all individuals with these factors appear to have the same risk of developing HCC. HCC exhibits a high degree of genetic heterogeneity: multiple molecular pathways may give rise to subsets of hepatocellular neoplasms. Previous work suggests an association between the Tyr113His and His139Arg mEH polymorphisms and susceptibility to hepatocellular carcinoma (HCC), but the results have been inconsistent
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