The causal effect of cytokine cycling levels on the risk of cervical cancer: A bidirectional 2-sample Mendelian randomization study

Increasing evidence suggests that inflammatory protein factors are closely associated with the underlying mechanisms of cervical cancer. Therefore, 2-sample Mendelian randomization (MR) analysis was performed to assess the potential correlation between circulating inflammatory protein levels and cervical cancer risk. A 2-sample MR study, using genetic variants related to inflammatory proteins as instrumental variables, was conducted to improve the accuracy of cervical cancer diagnosis. By analyzing 14,824 individuals, 91 plasma proteins having strong association with single nucleotide polymorphisms were chosen as instrumental variables, with cervical cancer (909 cases and 238,249 controls) serving as outcome variables. The analysis of causal effects was completed using random effect inverse variance weighted, weighted median/mode, and MR-Egger. Sensitivity analysis was performed using Cochran Q test, funnel plots, leave-one-out analyses, MR-Egger intercept tests, as well as reverse MR analysis. Our analysis showed that C-C motif chemokine ligand 19 (CCL19), monocyte chemotactic protein-3 (MCP-3), and interleukin-12 (IL-12) was related to the risk of cervical cancer. Additionally, the inverse variance weighted method indicated that both CCL19 (OR: 1.479, 95% CI: 1.207–1.813, P = .0002) and IL-12 (OR: 1.171, 95% CI: 1.019–1.345, P = .0253) significantly increased the risk of cervical cancer. Nevertheless, MCP-3 levels may protect individuals from developing cervical cancer (OR, 0.647; 95% CI: 0.442–0.947, P = .0253). Furthermore, consistent outcomes were achieved in the sensitivity analysis. In our study, MR analysis of 91 inflammatory proteins revealed potential causal associations between CCL19, MCP-3, IL-12, and the etiology of cervical cancer. We believe that related inflammatory proteins will provide potential treatment opportunities for clinical interventions in cervical cancer.