MMP1, 2, 3, 7, and 9 Gene Polymorphisms and Urinary Cancer Risk: A Meta-Analysis

Background: The matrix metalloproteinases (MMPs) are a family of highly conserved, metal-dependent proteolytic enzymes that play an important role in tumor invasion and metastasis. Many studies have been carried out on the association between polymorphisms in the MMP1, MMP2, MMP3, MMP7, and MMP9 genes and urinary cancer risk. However, the data from these published studies are conflicting and have low statistical power. Methods: In this study, we performed a meta-analysis of 12 different publications from the PubMed and WanFang databases, published up to May 2015, to better assess the purported associations. Odds ratios (OR) and 95% confidence intervals (CI) were determined to reveal association strengths. Results: Some significant associations were found. For the MMP1 -1607 1G/2G polymorphism, a negative association was identified for the 2G allele in bladder cancer (2G2G+2G1G vs. 1G1G: OR=0.57, 95% CI=0.36-0.93, p(heterogeneity)=0.001) and renal cell carcinoma (2G1G vs. 1G1G: OR=0.57, 95% CI=0.39-0.82, p(heterogeneity)=0.567). For the MMP2 -1306 C/T polymorphism, there was a negative association with the T allele for bladder cancer in the Asian population (TT+TC vs. CC: OR=0.41, 95% CI=0.18-0.94, p(heterogeneity)=0.195). For the MMP7 -181A/G polymorphism, a decreased bladder cancer risk was found (G-allele vs. A-allele: OR=0.81, 95% CI=0.66-0.98, p(heterogeneity)=0.325). Conclusion: In summary, our study showed evidence that genetic polymorphisms in MMP1 for all populations, but only in the Asian population for MMP2 and MMP7, may protect against bladder cancer risk. Future studies with larger sample sizes are warranted to further evaluate these associations in more detail.