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Meta-analysis of association between matrix metalloproteinases 2, 7 and 9 promoter polymorphisms and cancer risk
Bo Peng1, Lihuan Cao, Xiaopin Ma
1State Key Laboratory of Genetic Engineering, Department of Genetics, Institute of Genetics, School of Life Science, Fudan University, Shanghai, People's Republic of China.
Abstract:
Matrix metalloproteinase (MMP) 2, MMP7 and MMP9 are important members of the MMP family. Four polymorphisms in the promoter region of these MMPs, which are MMP2 -1306 C>T, MMP2 -735 C>T, MMP7 -181 A>G and MMP9 -1562 C>T, have been reported to be functional and may contribute to genetic susceptibility to cancers. However, the associations between these polymorphisms and cancer risk remain inconclusive due to conflicting results from different case-control studies. To better evaluate the role of these polymorphisms in cancer development, we conducted a meta-analysis that included 51 studies, with more than 40,000 subjects. The results showed that under dominant genetic model, MMP2 -1306 T was associated with lower susceptibility to lung cancer [odds ratio (OR) = 0.50, 95% confidence interval (CI) 0.43-0.59, P(heterogeneity) = 0.147, I(2) = 44.1%], head and neck cancer (OR = 0.53, 95% CI 0.41-0.69, P(heterogeneity) = 0.974, I(2) = 0.0%) and oesophageal cancer (OR = 0.67, 95% CI 0.55-0.80, P(heterogeneity) = 0.593, I(2) = 0.0%); MMP2-735T was associated with lower risk in lung cancer (OR = 0.65, 95%CI 0.53-0.79, P(heterogeneity) = 0.42, I(2) = 0.0%) and oesophageal cancer (OR = 0.84, 95% CI 0.70-0.99, P(heterogeneity) = 0.206, I(2) = 37.4%); MMP7 -181 AG and GG genotype carriers had an increased gastric cancer risk (OR = 1.90, 95% CI 1.43-2.51, P(heterogeneity) = 0.992, I(2) = 0.0%) and MMP9 -1562 C>T was not associated with cancer risk in the whole group analysis (OR = 0.99, 95% CI 0.91-1.08, P(heterogeneity) = 0.419, I(2) = 3.0%) and subgroup analyses. In all, our meta-analysis suggests that MMP2 -1306 C>T, MMP2 -735 C>T and MMP7 -181 A>G may play allele-specific roles in cancer development, while MMP9 -1562 C>T may not be a major risk factor for most cancer types. Large case-control studies should be performed to clarify the possible roles of these four polymorphisms in different kinds of cancer in more detail.
Insights
Matrix metalloproteinase (MMP) gene polymorphisms influence cancer risk. MMP2 and MMP7 variants are linked to reduced lung, head and neck, esophageal, and increased gastric cancer risks, respectively. MMP9 variants show no significant cancer association.
Area of Science:
- Genetics and Oncology
- Molecular Biology
- Cancer Epidemiology
Background:
- Matrix metalloproteinases (MMPs), including MMP2, MMP7, and MMP9, are crucial in cancer development.
- Specific promoter polymorphisms (MMP2 -1306 C>T, MMP2 -735 C>T, MMP7 -181 A>G, MMP9 -1562 C>T) are implicated in cancer susceptibility.
- Previous studies on these polymorphisms and cancer risk yield conflicting results, necessitating a comprehensive analysis.
Purpose of the Study:
- To conduct a meta-analysis evaluating the association between four functional MMP gene promoter polymorphisms and cancer risk.
- To clarify the role of MMP2, MMP7, and MMP9 polymorphisms in genetic susceptibility to various cancers.
Main Methods:
- A meta-analysis was performed, synthesizing data from 51 case-control studies.
- The analysis included over 40,000 subjects.
- Statistical methods, including odds ratios (OR) and confidence intervals (CI), were used to assess associations under dominant genetic models.
Main Results:
- MMP2 -1306 C>T polymorphism was associated with reduced risk for lung, head and neck, and esophageal cancers.
- MMP2 -735 C>T polymorphism showed a decreased risk for lung and esophageal cancers.
- MMP7 -181 A>G polymorphism (AG and GG genotypes) was linked to an increased risk of gastric cancer.
- MMP9 -1562 C>T polymorphism did not demonstrate a significant association with overall cancer risk.
Conclusions:
- MMP2 -1306 C>T, MMP2 -735 C>T, and MMP7 -181 A>G polymorphisms may play significant roles in cancer development.
- The MMP9 -1562 C>T polymorphism appears to be a minor risk factor for most cancer types studied.
- Further large-scale studies are recommended to elucidate the precise roles of these MMP polymorphisms in diverse cancers.