EGF rs4444903 polymorphism is associated with risk of HCV-related cirrhosis and HBV/HCV-related hepatocellular carcinoma

Objective The epidermal growth factor (EGF) rs4444903 polymorphism is associated with aberrant expression of EGF, which was a characteristic of cirrhotic liver diseases, induces highly malignant hepatocellular carcinoma (HCC). Numerous studies have uncovered the association of this polymorphism with the risk of liver disease, but with inconsistent findings. Materials and methods Therefore, this meta-analysis was performed to evaluate whether EGF rs4444903 polymorphism conferred susceptibility to liver disease. Totally 18 eligible articles were identified by searching PubMed, Google, CNKI and EMBASE up to December 1, 2020. Results Our results indicated that there was no significant difference in the minor G allele frequency of rs4444903 polymorphism between HBV/HCV carriers and healthy controls. In other words, EGF rs4444903 polymorphism was not associated with the risk of HBV/HCV. Interestingly, this polymorphism increased the risk of liver cirrhosis in the controls with HCV infection. Additionally, EGF rs4444903 polymorphism is associated with the increased risk of HCC under the five models. Subgroup analysis by ethnicity shows that rs4444903 polymorphism intensifies the risk of HCC among Asians and Caucasians. Strong correlation is also reported in controls with cirrhosis or HCV infection and studies using PCR-RFLP genotyping. Conclusions The study supports that EGF rs4444903 polymorphism is a genetic contributor to liver cirrhosis and HCC in the overall population. Nevertheless, this conclusion must be confirmed by larger studies with more diverse ethnic populations.

Automated summary

The EGF rs4444903 polymorphism does not significantly increase the risk of HBV/HCV, but is associated with increased risk of liver cirrhosis and HCC, particularly among Asians and Caucasians. Larger studies with diverse ethnic populations are needed to confirm these findings.