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
Summary
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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