STROBE-Cross-Population Mendelian Randomization Analysis of Circulating Inflammatory Proteins and Cervical Cancer Risk in European and Asian Populations.

Abstract

Objective: This study investigates the causal relationship between circulating inflammatory proteins and cervical cancer risk in European and Asian populations using Mendelian randomization (MR), providing insights into inflammation's role in cervical cancer pathogenesis.

Method: Data from 91 circulating inflammatory proteins from 11 cohorts (14,824 European participants, 909 cervical cancer cases, 238,249 controls; 605 cases, 89,731 controls in the Asian cohort) were analyzed. Inverse variance weighted (IVW) and MR-Egger methods were used to explore causal relationships. Sensitivity analyses, including Cochran's Q tests and leave-one-out analysis, ensured result reliability.

Results: In the European population, higher levels of CCL19, IL-1α, and IL-12B were associated with increased cervical cancer risk, while LIFR and PD-L1 were protective. In the Asian population, elevated CCL19, IL-1α, SLAM, and IL-10Rβ increased risk, while CXCL11, SULT1A1, and CXCL1 showed protective effects. Sensitivity analyses confirmed the robustness of these findings.

Conclusion: This study demonstrates a causal relationship between circulating inflammatory proteins and cervical cancer risk in both European and Asian populations. The findings highlight both pro-cancer and protective roles of specific inflammatory proteins, offering insights for biomarkers in cervical cancer risk assessment and prevention strategies.