Abstract
BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant liver cancer subtype with limited effective treatment options. Emerging evidence suggests that inflammatory factors play a critical role in ICC progression within the tumor microenvironment (TME). However, causal relationships between specific inflammatory factors and ICC risk remain unclear. AIM: To investigate the causal relationship between inflammatory factors and ICC. METHODS: This study used Mendelian randomization (MR) and Bayesian weighted MR (BWMR) analyses to investigate the causal impact of inflammatory factors on ICC risk. Genetic data from genome-wide association studies were utilized to identify and validate instrumental variables for 91 inflammatory factors, followed by sensitivity analyses to ensure robustness. RESULTS: MR analysis identified significant associations between elevated levels of artemin and matrix metalloproteinase (MMP)-10 and increased ICC risk. BWMR and meta-MR analysis results validated these associations. Sensitivity analyses confirmed the stability of these findings, indicating that specific inflammatory factors may contribute causally to ICC development. CONCLUSION: This study provides evidence that certain inflammatory factors, particularly artemin and MMP-10, are causally linked to ICC risk, identifying them as potential risk factors and therapeutic targeting. These findings enhance the understanding of the inflammatory components of the TME in ICC, supporting the development of targeted intervention strategies.