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

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.