No association of EGF 5'UTR variant A61G and hepatocellular carcinoma in Chinese patients with chronic hepatitis B virus infection

Pan, Qi; Wang, Hao; Chen, Yueming; Sun, Xuehua; Liang, Yan; Gao, Chunfang

doi:10.1080/00313020903071603

Cited by 23 publications

(42 citation statements)

References 31 publications

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“…Overall, 2,095 patients with HCC and 3,766 control individuals were retrieved. Seven of the studies enrolled Chinese individuals (15,(22)(23)(24)(25)(26), three studies involved a mixed population, including Caucasian, Hispanic and Asian populations and individuals of African descent (21,22,27), one study enrolled only Caucasians (21) and one enrolled only Egyptian individuals (28). The genotype distributions in the controls for all studies were consistent with the HWE expectations.…”

Section: Resultsmentioning

confidence: 63%

“…The publications by Zhong et al (15), Tanabe et al (21) and Yuan et al (22) all involved two independent case-control studies and were overall considered to be six single studies. Finally, a total of 12 studies (15,(21)(22)(23)(24)(25)(26)(27)(28) that examined the association between the EGF 61A/G polymorphism and the risk of HCC were included in the current meta-analysis (Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

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Quantitative assessment of the effect of epidermal growth factor 61A/G polymorphism on the risk of hepatocellular carcinoma

et al. 2015

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Abstract. The association between hepatocellular carcinoma (HCC) and the epidermal growth factor (EGF) 61A/G polymorphism has been analyzed in several studies, but results remain inconsistent. Therefore, the aim of the present study was to quantitatively summarize the association between the EGF 61A/G polymorphism and the risk of HCC. The PubMed and EMBASE databases were searched for studies published prior to May 1, 2014. The overall, subgroup and sensitivity analyses were conducted using Comprehensive Meta-Analysis software, version 2.2. In total, 12 published case-control studies, consisting of 2,095 patients with HCC and 3,766 control individuals, were included in the present study. Meta-analysis of the included studies revealed that EGF 61A/G polymorphism contributed to the risk of HCC under all four genetic models, consisting of the G vs. A (OR, 1.25; 95% CI, 1.11-1.40), GG vs. AA (OR, 1.53; 95% CI, 1.26-1.85), GG vs. AG + AA (OR, 1.34; 95% CI, 1.13-1.58) and GG + AG vs. AA (OR, 1.27; 95% CI, 1.08-1.49) comparisons. Subgroup analysis further suggested that EGF 61A/G polymorphism was associated with the risk of HCC in patients and control individuals with liver disease, based on ethnicity and source of control, respectively. No other significance in residual subgroup analysis was observed. The present meta-analysis suggests that the EGF 61A/G polymorphism is associated with an increased risk of HCC and may be a potential marker for liver disease, such as hepatitis B virus infection, hepatitis C virus infection and liver cirrhosis. IntroductionHepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and develops predominately in individuals with liver cirrhosis (1). Cirrhosis is the strongest known risk factor for HCC, particularly cirrhosis resulting from infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) (2,3). Additionally, heavy alcohol consumption, diabetes, obesity and tobacco use have been considered to contribute to the local burden of HCC (4,5). However, only a small number of people exposed to these risk factors develop HCC, suggesting that other environmental and genetic factors may play a role in HCC development. For this reason, the pathogenesis of HCC has not been fully elucidated.Additionally, numerous clinicians rely on serological α-fetoprotein testing and abdominal ultrasound imaging for HCC screening (6). However, these screening tools demonstrate low sensitivity and specificity (7-9) and the diagnoses of HCC are made late in the course of the disease. Therefore, early identification of molecular markers associated with an increased risk of HCC has been proposed as an alternative strategy for the diagnosis of HCC.Epidermal growth factor (EGF) was first isolated in 1962 (10) and plays a critical role in liver tissue regeneration (11). In previous years, numerous studies have revealed that the EGF signaling pathway with the EGF 61A/G polymorphism (rs4444903), a commonly functional single-nucleotide polymorphism (SNP) in the 5'-untranslated region of the EGF gen...

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Section: Resultsmentioning

confidence: 63%

Section: Resultsmentioning

confidence: 99%

Quantitative assessment of the effect of epidermal growth factor 61A/G polymorphism on the risk of hepatocellular carcinoma

et al. 2015

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“…The authors did not find a significant difference in EGF rs4444903 polymorphism allelic and genotypic frequencies between HBV patients with or without HCC. Moreover, the frequencies of chronic HBVinfected patients without HCC did not differ substantially from those of the healthy controls [18]. Finally, in patients with HCC, no significant association was detected between EGF rs4444903 polymorphism allelic frequencies and the severity of liver damage determined by the Child-Pugh score (score A versus score B + C).…”

Section: Yesmentioning

confidence: 80%

“…Although the EGF rs4444903 polymorphism has been repeatedly assessed in relation to HCC occurrence in patients with chronic HBV infection or in mixed cohorts, no study has been devoted to specifically ascertain whether this polymorphism could be implicated in the progression of liver fibrosis in patients with HBV chronic infection [15][16][17][18]. In the study of Li et al, no difference was detected in allelic and genotypic frequencies between control subjects and patients with liver cirrhosis, whereas the latter frequencies differed from those pertaining to patients affected by HCC [16].…”

Section: Yesmentioning

confidence: 99%

Carriage of the EGF rs4444903 A>G functional polymorphism associates with disease progression in chronic HBV infection

Cmet¹,

Fabris

Fattovich

et al. 2012

Clinical and Experimental Immunology

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SummaryBecause epidermal growth factor (EGF) up-regulation is characteristic of the cirrhotic liver, we hypothesised that the EGF rs4444903 A > G functional polymorphism might be associated with a worse disease course in patients with chronic HBV infection. To verify this hypothesis, 170 HBV-positive patients (125 males) with a median age of 52 years were studied. Sixty-two of these patients were followed longitudinally for a median time of 21 years. Genotyping for the EGF rs4444903 A > G polymorphism was performed by the polymerase chain reaction-based restriction fragment length polymorphism assay. In the cross-sectional study, the EGF rs4444903 A > G polymorphism genotypic frequencies significantly differed between transplant patients (A/A = 20·4%, A/G = 52·3%, G/G = 27·3%) and HBsAg+ carriers (active and inactive: A/A = 35·7%, A/G = 47·6%, G/G = 16·7%, P = 0·036 for the linear trend). In the longitudinal study, the EGF rs4444903 A > G polymorphism was found to be an independent predictor of cirrhosis development (O.R. 7·73, 95% C.I. 1·21-49·5, P = 0·007). Three groups of patients were identified: A/A female homozygotes (n = 9), A/A male homozygotes (n = 13) and carriers of the G allele of either gender (n = 40). Cirrhosis did not occur among A/A females (n = 0/9), seldom occurred among A/A males (n = 2/13) and reached the highest frequency among G/* patients (n = 13/40, P = 0·026). In conclusion, the EGF rs4444903 A > G polymorphism appears to be associated with an unfavourable disease course of chronic HBV infection and cirrhosis development. This effect might be modulated, at least in part, by the gender of the patient.

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“…The association studies between the EGF gene and HCC were mainly concentrated in the 61*A/G polymorphism (rs4444903), however, the results are inconsistent (Li et al, 2009;Qi et al, 2009;Zhong et al, 2012). In this study, we aim to investigate the association between polymorphisms in the EGFR gene and its ligand EGF gene and hepatitis B virus (HBV)-related HCC in the Chinese Han population.…”

Section: Introductionmentioning

confidence: 99%

Association of Epidermal Growth Factor and Epidermal Growth Factor Receptor Polymorphisms with the Risk of Hepatitis B Virus-Related Hepatocellular Carcinoma in the Population of North China

Zhang

et al. 2013

Genetic Testing and Molecular Biomarkers

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Background: Hepatocellular carcinoma (HCC) is a common solid malignant tumor occurring worldwide that leads to the third largest cause of death compared to other cancers. Genetic and environmental factors are involved in the pathogenesis of HCC. Epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) can stimulate the proliferation of epidermal and epithelial cells. The EGF signal pathway has a relationship with the growth of the embryo, tissue repairing, and tumorigenesis. Methods: In this study, 416 patients with hepatitis B virus infection (HBV)-related HCC and 645 individuals who had never been infected with HBV of the Chinese Han population were enrolled. Eight single-nucleotide polymorphisms (SNPs), whose minor allele frequency > 20% in the EGF and EGFR genes, were genotyped to examine their associations with hepatocarcinogenesis. Genotyping experiments were carried out using TaqMan. Results: There were significant differences in genotype distributions ( p = 0.005) and allele frequencies ( p = 0.001, odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.15-1.79) of rs11569017 in the EGF gene between the HCC and control groups. After binary logistic regression to determine independent factors for susceptibility to HCC under an additive model, rs11569017 was still independently associated with the susceptibility to HCC ( p = 0.021, OR = 1.48, 95% CI = 1.06-2.07), but no significant differences in other SNPs were found. Additionally, the haplotype T-G constructed by rs11569017 and rs4444903 of the EGF gene might increase the risk of HBV-related HCC ( p = 0.002, OR = 1.44, 95% CI = 1.15-1.82). Conclusion: The rs11569017 T allele was associated with susceptibility to HBV-related HCC.

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No association of EGF 5'UTR variant A61G and hepatocellular carcinoma in Chinese patients with chronic hepatitis B virus infection

Cited by 23 publications

References 31 publications

Quantitative assessment of the effect of epidermal growth factor 61A/G polymorphism on the risk of hepatocellular carcinoma

Quantitative assessment of the effect of epidermal growth factor 61A/G polymorphism on the risk of hepatocellular carcinoma

Carriage of the EGF rs4444903 A>G functional polymorphism associates with disease progression in chronic HBV infection

Association of Epidermal Growth Factor and Epidermal Growth Factor Receptor Polymorphisms with the Risk of Hepatitis B Virus-Related Hepatocellular Carcinoma in the Population of North China

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No association of EGF 5'UTR variant A61G and hepatocellular carcinoma in Chinese patients with chronic hepatitis B virus infection

Cited by 23 publications

References 31 publications

Quantitative assessment of the effect of epidermal growth factor 61A/G polymorphism on the risk of hepatocellular carcinoma

Quantitative assessment of the effect of epidermal growth factor 61A/G polymorphism on the risk of hepatocellular carcinoma

Carriage of the EGF rs4444903 A&gt;G functional polymorphism associates with disease progression in chronic HBV infection

Association of Epidermal Growth Factor and Epidermal Growth Factor Receptor Polymorphisms with the Risk of Hepatitis B Virus-Related Hepatocellular Carcinoma in the Population of North China

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Carriage of the EGF rs4444903 A>G functional polymorphism associates with disease progression in chronic HBV infection