Abstract
BACKGROUND: Chronic hepatitis B virus (HBV) infection is a major global health concern, contributing to both hepatic and extrahepatic complications, including cancer. While its association with liver cancer is well established, the role of HBV in extrahepatic malignancies remains less clear. This study aimed to investigate the potential causal relationship between chronic HBV infection and common extrahepatic cancers. METHODS: We applied Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data to assess causal links between chronic HBV infection and extrahepatic cancer risk. Transcriptomic data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to identify differentially expressed genes (DEGs) and explore potential mechanisms. RESULTS: MR analysis revealed a significant causal association between chronic HBV infection and increased risks of breast and lung cancers. Key DEGs, including SPP1 and PDK4, were identified, implicating molecular pathways involved in tumor progression. CONCLUSION: Our findings indicate a modest but significant link between chronic HBV infection and elevated extrahepatic cancer risk, highlighting potential therapeutic targets for HBV-infected individuals. These results support the need for personalized monitoring and treatment strategies in precision oncology.