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The association between MMP-12 82 A/G polymorphism and susceptibility to various malignant tumors: a meta-analysis
Sheng-Song Chen1, Juan Song1, Xiao-Yun Tu1
1Department of Respiratory Diseases, The Second Affiliated Hospital of Nanchang University Nanchang 330006, China.
Abstract:
Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases responsible for degrading essentially all components of the extracellular matrix (ECM). Accumulating evidence suggests that MMPs might play a critical role in growth, invasion, and metastasis of malignant tumors. A single nucleotide polymorphism (SNP) in the promoter region of MMP-12, MMP-12 82 A/G (rs2276109), has been recognized to play a critical role in regulating the expression of MMP-12, however, its correlation with tumor susceptibility remains controversial. To address this issue, we performed meta-analysis to investigate the association MMP-12 82 A/G polymorphism and susceptibility of nine malignant tumors from 11 studies, including 6153 cancer patients and 6838 controls. Two reviewers independently screened studies for eligibility and extracted data for included studies. While overall no evident association between MMP-12 82 A/G and tumor susceptibility was observed, subgroup analysis revealed a specific role of G allele in increasing the susceptibility for epithelial ovarian carcinoma (EOC) using the allele model (fixed effects OR = 2.45, 95% CI = 1.46-4.10, P = 0.001) and the dominant model (fixed effects OR = 2.52, 95% CI = 1.49-4.24, P = 0.001). We thus suggest that G allele of MMP-12 82 A/G polymorphism is a genetic risk factor for EOC.
Insights
The MMP-12 82 A/G polymorphism is not linked to overall cancer risk. However, the G allele of this single nucleotide polymorphism (SNP) increases susceptibility to epithelial ovarian carcinoma (EOC).
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- Matrix metalloproteinases (MMPs) degrade extracellular matrix components.
- MMPs are implicated in tumor growth, invasion, and metastasis.
- The MMP-12 82 A/G (rs2276109) single nucleotide polymorphism (SNP) influences MMP-12 expression, but its link to cancer susceptibility is debated.
Purpose of the Study:
- To investigate the association between the MMP-12 82 A/G polymorphism and susceptibility to nine types of malignant tumors.
- To clarify the controversial role of this specific MMP-12 SNP in cancer development.
Main Methods:
- A meta-analysis was conducted on 11 studies.
- Data from 6153 cancer patients and 6838 controls were analyzed.
- Two independent reviewers screened studies and extracted relevant data.
Main Results:
- No overall association was found between the MMP-12 82 A/G polymorphism and susceptibility to the nine studied tumors.
- Subgroup analysis revealed the G allele significantly increases susceptibility to epithelial ovarian carcinoma (EOC).
- The G allele showed increased risk in both allele (OR=2.45) and dominant (OR=2.52) models for EOC.
Conclusions:
- The MMP-12 82 A/G polymorphism does not appear to be a general risk factor for the nine common cancers studied.
- The G allele of the MMP-12 82 A/G polymorphism is identified as a specific genetic risk factor for epithelial ovarian carcinoma (EOC).
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