Correlation of DEPDC5 rs1012068 and rs5998152 Polymorphisms with Risk of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Abstract

Background. Emerging evidence has shown that two common genetic polymorphisms within the pleckstrin domain-containing protein 5 (DEPDC5), rs1012068 and rs5998152, may be associated with the risk of hepatocellular carcinoma (HCC), especially in those individuals chronically infected with the hepatitis C virus (HCV) or the hepatitis B virus (HBV). However, these findings have not been consistently replicated in the literature due to limited sample sizes or different etiologies of HCC. Thus, the present systematic review and meta-analysis were performed to resolve this inconsistency. Methods. The databases PubMed, Embase, Web of Science, the China National Knowledge Infrastructure, and Scopus were searched up to December 12, 2022. Data from relevant studies were pooled, and odds ratios and 95% confidence intervals were calculated. Results. A total of 11 case-control studies encompassing 2,609 cases and 8,171 controls on rs1012068 and three encompassing 411 cases and 1,448 controls on rs5998152 were included. Results indicated that the DEPDC5 rs1012068 polymorphism did not significantly increase HCC risk in the total population (allelic model (OR = 1.32, 95% CI = 1.04–1.67, P = 0.02); the recessive model (OR = 1.42, 95% CI = 0.96–2.10, P = 0.08); the dominant model (OR = 1.43, 95% CI = 1.09–1.87, P = 0.01); the homozygous model (OR = 1.61, 95% CI = 1.01–2.57, P = 0.05); the heterozygous model (OR = 1.39, 95% CI = 1.09–1.79, P = 0.009)). Subgroup analyses based on ethnicity and etiology revealed that the rs1012068 polymorphism, under all five genetic models, was associated with increased HCC risk in Asians or in individuals with chronic HBV infection but not in individuals with chronic HCV infection. A significant association was also observed between rs5998152 and HCV-related HCC risk in Asians chronically infected with HCV under allelic, dominant, and heterozygous models. Conclusion. Our study suggests that the DEPDC5 rs1012068 polymorphism increases HCC risk, especially in Asians with chronic HBV infection, while the rs5998152 polymorphism increases HCC risk in Asians with chronic HCV infection.

HBV Infection and Host Interactions: The Role in Viral Persistence and Oncogenesis

“…Compared with non-cirrhotics, HBV-related cirrhotic patients show a 31-fold increased risk of HCC [78]. Injury cofactors (e.g., coinfection with HDV, alcohol consumption), comorbidities (e.g., diabetes mellitus), or gene polymorphisms (e.g., PNPLA3 or DEPDC5 polymorphisms) can accelerate the progression of liver fibrosis and the development of neoplasms [79][80][81][82]. These oncogenic mechanisms link HBV infection to other etiologies of chronic liver damage (viral, metabolic, exotoxic, autoimmune) [77,83,84].…”