Abstract: Objective To explore the causal relationship between peripheral blood metal element levels and cervical cancer based on large-scale human genetic data from Genome-Wide Association Study (GWAS) databases, using Mendelian randomization (MR) analysis methods. Methods Data sets for 21 peripheral blood metal elements were obtained from the GWAS Catalog database as exposure data, while GWAS data for cervical cancer were obtained from the FinnGen database as outcome data. A two-sample MR analysis method was used to assess the potential causal relationship between peripheral blood metal element levels and cervical cancer. The inverse variance weighted (IVW) method was employed as the primary analysis approach to estimate the relationship between exposure (i.e., peripheral blood metal elements) and outcome (i.e., cervical cancer) using multiple instrumental variables (IVs), thereby obtaining more precise causal effect estimates. Weighted median analysis, weighted mode, and MR-Egger methods were also used to complement the analysis, ensuring the reliability of causal inference and the robustness of the results. Additionally, heterogeneity and horizontal pleiotropy analyses were conducted, and the MR Steiger directionality test was used to exclude reverse causality. Results The IVW analysis showed that serum nickel levels were positively associated with the risk of cervical malignancy (OR=1.145, 95% CI: 1.008-1.300, P=0.037). This causal relationship was not affected by heterogeneity (Q_MREgger=40.211, P_MR-Egger= 0.505; Q_IVW=40.288, P_IVW=0.546) or horizontal pleiotropic effects (MR-Egger intercept=0.00889, P=0.784). Serum molybdenum levels were found to be a protective factor for squamous cell carcinoma of the cervix (OR=0.810, 95% CI: 0.658~0.997, P=0.047). Sensitivity analyses and other MR analyses also indicated no heterogeneity, horizontal pleiotropy, or reverse causality in the study results. Conclusion sSerum nickel and molybdenum levels have genetically predicted causal relationships with the occurrence of cervical cancer. These findings provide a new perspective for predicting the development and progression of cervical cancer and may aid in the prevention and early diagnosis of this disease.

Key words: Cervical cancer, Trace elements, Metal elements, Mendelian randomization, Causal relationship