Abstract

BackgroundHepatocarcinogenesis is a complex process that may be influenced by many factors, including polymorphism in the epidermal growth factor (EGF) gene. Previous work suggests an association between the EGF 61*A/G polymorphism (rs4444903) and susceptibility to hepatocellular carcinoma (HCC), but the results have been inconsistent. Therefore, we performed a meta-analysis of several studies covering a large population to address this controversy.MethodsPubMed, EMBASE, Google Scholar and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. Data were abstracted independently by two reviewers. A meta-analysis was performed to examine the association between EGF 61*A/G polymorphism and susceptibility to HCC. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.ResultsEight studies were chosen in this meta-analysis, involving 1,304 HCC cases (1135 Chinese, 44 Caucasian and 125 mixed) and 2,613 controls (1638 Chinese, 77 Caucasian and 898 mixed). The EGF 61*G allele was significantly associated with increased risk of HCC based on allelic contrast (OR = 1.29, 95% CI = 1.16–1.44, p<0.001), homozygote comparison (OR = 1.79, 95% CI = 1.39–2.29, p<0.001) and a recessive genetic model (OR = 1.34, 95% CI = 1.16–1.54, p<0.001), while patients carrying the EGF 61*A/A genotype had significantly lower risk of HCC than those with the G/A or G/G genotype (A/A vs. G/A+G/G, OR = 0.66, 95% CI = 0.53–0.83, p<0.001).ConclusionThe 61*G polymorphism in EGF is a risk factor for hepatocarcinogenesis while the EGF 61*A allele is a protective factor. Further large and well-designed studies are needed to confirm this conclusion.

Highlights

  • As the most frequent primary cancer of the liver, hepatocellular carcinoma (HCC) is the fifth most common solid tumor worldwide and the third leading cause of cancer-related deaths, exceeded only by lung cancer and gastric cancer [1]

  • Inclusion criteria A study was included in the meta-analysis if it satisfied the following criteria: (a) it assessed the correlation between HCC and the epidermal growth factor (EGF) 61*A/G polymorphism, (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 EGF 61*A/G polymorphism and HCC based on the genotype frequencies in cases and controls

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Summary

Introduction

As the most frequent primary cancer of the liver, hepatocellular carcinoma (HCC) is the fifth most common solid tumor worldwide and the third leading cause of cancer-related deaths, exceeded only by lung cancer and gastric cancer [1]. The estimated incidence of new HCC cases each year is approximately 500 000– 1 000 000, and it causes 600 000 deaths globally each year [1]. HCC exhibits a high degree of genetic heterogeneity: multiple molecular pathways may give rise to subsets of hepatocellular neoplasms [5]. For this reason, HCC pathogenesis remains incompletely understood. Previous work suggests an association between the EGF 61*A/G polymorphism (rs4444903) and susceptibility to hepatocellular carcinoma (HCC), but the results have been inconsistent.

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