AUTHOR=Yang Yusha , Jiang Zufu , Wu Weizhou , Ruan Libin , Yu Chengyang , Xi Yuning , Wang Liling , Wang Kunpeng , Mo Jinggang , Zhao Shankun TITLE=Chronic Hepatitis Virus Infection Are Associated With High Risk of Gastric Cancer: A Systematic Review and Cumulative Analysis JOURNAL=Frontiers in Oncology VOLUME=Volume 11 - 2021 YEAR=2021 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.703558 DOI=10.3389/fonc.2021.703558 ISSN=2234-943X ABSTRACT=Mounting studies demonstrated both chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) infection might be associated not only with an increased risk of hepatocellular carcinoma but also extrahepatic malignancies, i.e., gastric cancer (GC). However, a quantitative result addressing the association between HBV/HCV infection and GC development is scarce. A systematic searching to identify the eligible studies was performed in the four databases, including MEDLINE, EMBASE, Cochrane Library, and the PsychINFO. The relationship between HBV/HCV infection and the risk of GC was quantified by calculating the hazard ratio (HR) with a 95% confidence interval (CI). More methodologies of this study were available in the PROSPERO (ID: CRD42021243719). Thirteen included studies involving 7,027,546 individuals (mean age: 42.6-71.9 years) were enrolled in the pooled analyses. Two articles provided the clinical data of both HBV and HCV infection. The proportion of high methodological quality studies was 76.9% (10/13). Synthetic results from 10 eligible studies of HBV showed that HBV infection was associated with a significantly higher risk of GC when compared to the healthy controls without HBV infection (pooled HR= 1.26, 95%CI: 1.08 to 1.47, P=0.003; heterogeneity: I2= 89.3%, P< 0.001). In line with this finding, the combined effect derived from 5 included studies of HCV also supported a significant positive association between chronic HBV infection and GC development (pooled HR = 1.88, 95%CI: 1.28-2.76, P = 0.001; heterogeneity: I2 = 74.7%, P = 0.003). In conclusion, both chronic HBV and HCV infection were related to a high risk of GC. The plausible mechanisms underlying such association might be correlated to HBV/HCV infection-induced persistent inflammation, immune dysfunction, and cirrhosis.