Association of inflammation-related cytokines and immune cells on bladder cancer：A mendelian-randomization study

Background The inflammation-immune response is thought to be closely related to cancer. Although several studies have evaluated the potential prognostic value of inflammation-immune response in cancer over the past few decades, their effects on patients with bladder cancer (BCa) has not been thoroughly reported. Methods A two sample mendelian randomization (MR) analysis was performed to analyze the relationship among 91 inflammation-related cytokines, 731 immune cells and BCa in genome-wide association studies. Inverse-variance weighted (IVW) random-effects models were used to examine the relationship between genetic suppression of these exposure factors and BCa risk. Cochran’s Q test, MR-Egger intercept test, and leave-one-out sensitivity analyses were conducted to evaluate the heterogeneity, horizontal pleiotropy, and stability of single-nucleotide polymorphisms in BCa. Results Based on the results of MR analysis, we identified 4 inflammation-related cytokines (Neurotrophin-3, IL-2Rβ, 5-hydroxytrptamine and E-selectin) that contributed to poorer outcomes in patients with BCa. In addition, there were 17 immune cells that may play a causal role in BCa. Of these, 9 immune cells and their subtypes were associated with an increased risk of BCa, and 8 were negatively associated with BCa risk. These 8 immune cells belong to HLA DR + T cell subtype, which is a beneficial factor in BCa. Conclusions Through genome-wide association studies, we discovered the key involvement of inflammation-related cytokines and immune cells in the coordination of the inflammatory-immune response in BCa. We demonstrated a range of cytokines and immune cell populations that can serve not only as important diagnostic indicators for BCa, but also as key targets for the development of new treatment and prevention strategies.