Causal Relationship Between Matrix Metalloproteinase and Cervical Lesions: A Two-Sample Mendelian Randomization Analysis.

Abstract

Purpose: This study aimed to investigate the causal relationship between matrix metalloproteinases (MMPs) and cervical lesions, as their correlation remains unclear despite reports of their involvement in the pathogenesis of these lesions.

Patients and methods: A two-sample Mendelian randomization (MR) analysis was performed using genome-wide association studies (GWAS) summary data to assess the causal associations of MMPs (MMP-1, 2, 3, 7, 9, 10, 12, 14, 16, and 17) with cervical lesions. The primary analysis utilized the inverse-variance weighted (IVW) method, supplemented by weighted median, mode, and MR-Egger regression. Heterogeneity was evaluated using Cochran's Q test and Leave-one-out analysis, while MR-Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) methods addressed horizontal pleiotropy.

Results: IVW analysis revealed causal effects of MMP-3 on cervical precancerous lesions (OR = 0.9993, P=0.0248), MMP-7 on cervical cancer (OR=0.6131, P = 0.0303), MMP-9 on cervical inflammation (OR = 1.1081, P = 0.0446), and MMP-12 on cervical erosion (OR = 0.8354, P = 0.0444), and cervical cancer (OR = 0.6836, P = 0.006). Sensitivity analyses confirmed these findings.

Conclusion: The study highlights causal associations between MMPs and cervical lesions, suggesting their potential as therapeutic targets and biomarkers for early detection. Future research should further explore the mechanisms involved.