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

Mingxing Pan1, Wei Tian2, Meiling Su3

  • 1Digestive Endoscopy Center, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, Heilongjiang, People's Republic of China.

International Journal of Women'S Health
|August 27, 2025
PubMed
Abstract

Insights

This study used Mendelian randomization to find causal links between matrix metalloproteinases (MMPs) and cervical lesions. Certain MMPs show potential as biomarkers for cervical precancerous lesions and cancer.

Area of Science:

  • Genetics and Molecular Biology
  • Oncology
  • Women's Health

Background:

  • Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of various lesions.
  • The precise causal relationship between specific MMPs and cervical lesions remains unclear.
  • Understanding these associations is crucial for developing targeted therapies and diagnostic tools.

Purpose of the Study:

  • To investigate the causal associations between a panel of matrix metalloproteinases (MMPs) and various cervical lesions.
  • To clarify the role of MMPs in the development and progression of cervical diseases.
  • To identify potential MMP-based biomarkers for cervical lesion detection and treatment.

Main Methods:

  • A two-sample Mendelian randomization (MR) analysis was conducted using genome-wide association studies (GWAS) summary data.
  • Investigated causal effects for MMP-1, -2, -3, -7, -9, -10, -12, -14, -16, and -17.
  • Employed inverse-variance weighted (IVW) method, supplemented by sensitivity analyses (weighted median, MR-Egger, MR-PRESSO) to ensure robustness and assess pleiotropy.

Main Results:

  • Significant causal associations were identified between specific MMPs and cervical lesions.
  • MMP-3 showed a causal effect on cervical precancerous lesions.
  • MMP-7 and MMP-12 were associated with cervical cancer, while MMP-9 linked to cervical inflammation and MMP-12 to cervical erosion. Sensitivity analyses validated these findings.

Conclusions:

  • This study provides evidence for causal links between several matrix metalloproteinases and cervical lesions.
  • These findings suggest that MMPs could serve as potential therapeutic targets and biomarkers for early detection of cervical diseases.
  • Further research is warranted to elucidate the underlying biological mechanisms connecting MMPs and cervical pathology.
Keywords:
Mendelian randomizationSNPscausal relationshipcervical lesionsgenetic associationmatrix metalloproteinase

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