epidermal-growth-factor and Hepatitis-B--Chronic

Because 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.

Topics: 5' Untranslated Regions; Adolescent; Adult; Aged; Aged, 80 and over; Alleles; Cross-Sectional Studies; Disease Progression; Epidermal Growth Factor; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Hepatitis B, Chronic; Humans; Liver Cirrhosis; Male; Middle Aged; Polymorphism, Single Nucleotide; Retrospective Studies; Sex Factors; Young Adult

Chronic hepatitis B virus (HBV) infection is a risk factor of hepatocellular carcinoma (HCC) in China. Epidermal growth factor (EGF) plays an important role in tumorigenesis. The association between EGF +61 G/A polymorphism and the risk of HCC is still controversial and ambiguous.. The objective of this study was to investigate the association between EGF +61 G/A polymorphism and the risk of HCC in a Chinese population.. A hospital-based case-control study was designed in a Chinese population. EGF +61 G/A polymorphisms were determined in 120 chronic HBV-infected HCC patients, 120 chronic HBV-infected cirrhotic patients, and 120 healthy controls. The genotype frequency of this polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism assay.. EGF +61 GG (odds ratio=2.76, 95% confidence interval=1.03, 7.38; p=0.04) and G allele frequencies (odds ratio=1.59, 95% confidence interval=1.08, 2.34; p=0.02) in the HCC group were higher than those in the cirrhosis group. EGF +61 A and G allele frequencies in healthy subjects were 28.8% and 71.2%. No relationship between EGF +61 G/A gene polymorphism and HCC risk was found among our recruited HCC patients and healthy controls.. This study suggests that EGF +61 GG genotype is associated with a higher risk of chronic HBV-infected HCC in the Chinese population.

Topics: Aged; Asian People; Carcinoma, Hepatocellular; Case-Control Studies; China; Epidermal Growth Factor; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Hepatitis B virus; Hepatitis B, Chronic; Humans; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Polymorphism, Genetic; Risk Factors

Chronic hepatitis B virus (HBV) infection is an important risk factor for hepatocellular carcinoma (HCC) development in China, while little is known of the genetic susceptibility to hepatocarcinogenesis. The epidermal growth factor (EGF) pathway plays an important role in tumorigenesis, including HCC. EGF polymorphisms are associated with susceptibility to several types of cancers. Therefore, this study aimed to assess whether EGF genetic polymorphisms can influence HCC development.. A total of 338 chronic HBV-infected patients (186 HCC patients and 152 cirrhotic patients) and 186 healthy individuals were enrolled in this study. EGF 61A/G polymorphisms of all subjects and 12 cell lines were assayed with polymerase chain reaction-restriction fragment length polymorphism and the sequencing method. Furthermore, EGF protein levels were measured in the serum and the results were compared with the different genotypes. EGF expression in the liver tissue of the HCC patients was detected by immunohistochemical analysis.. EGF 61A and 61G allele frequencies in healthy subjects were 28.76 and 71.24%. EGF 61GG and G allele frequencies in the HCC group were higher than those in the cirrhosis group. EGF protein levels with the GG genotype were significantly higher than those with either the GA or the AA genotype. About 59.09% of HCC liver tumour tissues assayed showed EGF protein expression.. The EGF 61 GG genotype might be associated with a high risk for the development of chronic HBV infection-related HCC in Chinese patients.

Topics: Adult; Aged; Aged, 80 and over; Asian People; Carcinoma, Hepatocellular; Cell Line, Tumor; DNA Mutational Analysis; Epidermal Growth Factor; Female; Gene Frequency; Genetic Predisposition to Disease; Hepatitis B virus; Hepatitis B, Chronic; Humans; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Risk Factors; Young Adult

Epidermal growth factor (EGF) has many biological functions, including mitogenesis, tumorigenesis, and proliferation of epidermal tissues. Previous studies have reported that the EGF +61 (A/G) single nucleotide polymorphism in the 5'-untranslated region of the EGF gene is functional, and is associated with development of hepatocellular carcinoma (HCC) in liver cirrhosis and various malignancy. Our aim was to investigate whether EGF gene A61G polymorphism could be implicated in susceptibility to and/or clinicopathological characteristics of HCC in Chinese patients with chronic hepatitis B virus (HBV) infection.. This polymorphism was studied in 387 patients with chronic HBV infection and in 208 healthy volunteers using restriction fragment-length polymorphism. The patients were divided into two groups: those without (n = 172) and those with HCC (n = 215). These 215 HCC patients with chronic HBV infection were designated as cases, and the remaining 172 patients without HCC served as controls.. There were no significant differences in EGF genotype or allelic frequencies between cases and controls nor was EGF genotype or allelic frequencies associated with tumour number, size, growth phase, stage, and invasiveness. We also found ethnic heterogeneity in the functional EGF polymorphism.. The present results show that although EGF gene A61G polymorphism is associated with development of HCC in liver cirrhosis, it is not sufficient for HCC in Chinese patients with chronic HBV infection.

Topics: 5' Untranslated Regions; Carcinoma, Hepatocellular; Epidermal Growth Factor; Female; Genetic Predisposition to Disease; Genotype; Hepatitis B virus; Hepatitis B, Chronic; Humans; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Polymorphism, Single Nucleotide

Strong interest exists about the biomolecular basis of the chronic liver diseases due to viral infections. It seems to be very interesting because of their evolutive potential. In this context the study of oncogenes and oncoproteins could be interesting as prognostic factors for chronic viral diseases of the liver. In this study the authors show the results obtained about EGF and p62 expression in 39 selected patients with cirrhosis and 3 different chronic viral hepatitis (persistent, lobular, and active).

Topics: Biomarkers, Tumor; Biopsy; Chronic Disease; Epidermal Growth Factor; Hepatitis B, Chronic; Hepatitis C, Chronic; Hepatitis, Viral, Human; Hepatocytes; Humans; Liver; Liver Cirrhosis; Prognosis; Proto-Oncogene Proteins c-myc; Receptor, ErbB-2