Association between epidermal growth factor 61A/G polymorphism and hepatocellular carcinoma susceptibility in Chinese patients

Abstract

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.