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Epidemiological Evidence Between Variants in Matrix Metalloproteinases-2, -7, and -9 and Cancer Risk
Chenglu Huang1, Suqin Xu2, Zhilin Luo1
1Department of Thoracic Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Background:
Matrix metalloproteinases (MMPs), a kind of proteases, have a critical function in cancer occurrence, invasion, and migration. MMP gene variants (e.g., MMP-2, MMP-7, and MMP-9) can affect the biological functions of these enzymes and lead to the occurrence and progression of cancer, which has become a hot topic in recent years, but the corresponding results are still controversial. In this context, here, the meta-analysis was conducted for assessing the relations of variants in MMP-2, MMP-7, and MMP-9 with the risk of various cancers.
Methods:
PubMed, Web of Science, and Medline were systemically searched, and data were extracted from all eligible studies so as to investigate the susceptibility of MMP-2, MMP-7, and MMP-9 to different types of cancers. The association between a variant in MMP and cancer susceptibility was analyzed through odds ratios (ORs) as well as 95% CIs. The Venice criteria and false-positive report probability (FPRP) were adopted to evaluate epidemiological evidence of significant associations discovered.
Results:
The associations between the variants of MMPs and cancer risk in 36,530 cases and 41,258 controls were found, with 12 associations (MMP-2 rs243865 with esophageal cancer and lung cancer, MMP-7 rs11568818 with bladder and cervical cancer, and MMP-9 rs3918242 with breast cancer) rated as strong associations for cancer risk and 7 and 15 as moderate and weak associations, respectively. These significant associations were mostly found in Asians.
Conclusions:
These findings support the relations between variants of MMP-2, MMP-7, and MMP-9 and various cancers risk, demonstrating the credibility of these relations.
Insights
Genetic variants in matrix metalloproteinases (MMPs), specifically MMP-2, MMP-7, and MMP-9, are linked to various cancer risks. This meta-analysis confirms these associations, particularly in Asian populations.
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- Matrix metalloproteinases (MMPs) play a crucial role in cancer development, invasion, and metastasis.
- Genetic variations in MMP genes (MMP-2, MMP-7, MMP-9) can influence enzyme function and impact cancer susceptibility and progression.
- Previous studies on MMP gene variants and cancer risk have yielded controversial results, necessitating further investigation.
Approach:
- A comprehensive meta-analysis was conducted by systematically searching PubMed, Web of Science, and Medline databases.
- Data from eligible studies were extracted to assess the association between MMP-2, MMP-7, and MMP-9 variants and susceptibility to various cancers.
- Odds ratios (ORs) with 95% CIs were used to analyze the associations, with the Venice criteria and FPRP employed for evidence evaluation.
Key Points:
- The meta-analysis identified 12 strong associations between MMP variants and cancer risk, including MMP-2 rs243865 with esophageal and lung cancer, MMP-7 rs11568818 with bladder and cervical cancer, and MMP-9 rs3918242 with breast cancer.
- Seven moderate and fifteen weak associations were also found, indicating a spectrum of influence from these genetic variants.
- Significant associations were predominantly observed in Asian populations, suggesting potential ethnic-specific effects.
Conclusions:
- The findings provide robust support for the relationship between variants in MMP-2, MMP-7, and MMP-9 genes and the risk of developing various cancers.
- These validated associations enhance the credibility of MMP genetic variants as potential biomarkers for cancer risk assessment.
- Further research may elucidate the precise mechanisms underlying these associations and their clinical implications.
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