COVID-19, inflammatory cytokines, and digestive system cancers: a bidirectional Mendelian study and mediation analysis

Gastrointestinal cancers pose a significant global health burden, contributing to 8% of cancer cases and a substantial number of deaths each year. Meanwhile, the Corona Virus Disease 2019(COVID-19) pandemic has potentially elevated the risk of digestive system cancers (DSCs), and this work aims to investigate the causal relationship between COVID-19 infection andDSCs, and the role of inflammatory cytokines (IC). This study employs a two-sample mendelian randomization (MR) approach, using COVID-19, ICs, and DSCs single-nucleotide polymorphisms (SNPs) as instrumental variables to investigate their causal relationship. The primary outcome is assessed using the inverse variance-weighted method. Moreover, mediation analysis was conducted using Two-step method. This work revealed that COVID-19 infection increases the susceptibility of malignant stomach neoplasm and benign small intestine neoplasm, while malignant colorectal cancer and biliary tract neoplasm increase COVID-19 susceptibility. Additionally, 32 ICs were linked to 12 DSCs and 13 ICs associated with all COVID-19 outcomes. There is a bidirectional causal relationship between COVID-19 and DSCs. ICs are closely associated with both COVID-19 and DSCs, but their mediating role has been overstated in previous studies.