Genetic polymorphisms of matrix metalloproteinase-1 is associated with the risk of cancer metastasis : an update meta-analysis

Background: Matrix metalloproteinase-1 is the most expressed interstitial collagenase among Matrix me­talloproteinases (MMPs), which play a central role in the degradation of basement membranes and the extracel­lular matrix. Accumulating evidences have elucidated that the genetic polymorphisms of Matrix metalloproteinase-1 (MMP-1) were associated with cancer invasion and metastasis with inconsistent results. To derive a more precise and reliable evaluation of the relationship between MMP-1(-1607)1G/2G polymorphism and cancer metastasis, we carried out this comprehensive meta-analysis. Methods: A systematic search of PubMed, EMBASE and Web of Science was conducted for relevant studies. A total of twenty-three eligible studies were included in this meta-analysis. The odds ratios (ORs) with 95% confidence intervals (95% CIs) calculated by Stata software were used to assess the associations between MMP-1(-1607)1G/2G polymorphism and cancer metastasis. We used Q test, I2 value, and funnel plot to examine heterogeneity and publication bias, respectively. Results: Twenty-three studies containing 3208 cancer cases (1546 metastasis-positive cases and 1662 metastasis-negative cases) were pooled together in this meta-analysis. The results showed that MMP-1(-1607)1G/2G polymorphism was significantly asso­ciated with the increased risk of cancer metastasis (dominant model: 2G2G + 1G2G vs. 1G1G, OR = 1.28, 95% CI = 1.01-1.62, P = 0.040; recessive model: 2G2G vs. 1G2G + 1G1G, OR = 1.34, 95% CI = 1.02-1.76, P = 0.040; allele model: 2G vs. 1G, OR = 1.27, 95% CI = 1.11-1.45, P < 0.001). Stratified analysis based on ethnicity revealed that MMP-1(-1607)1G/2G polymorphism significantly increased the risk of cancer metastasis in Europeans. Besides, no obvious publication bias was observed in the analysis. Conclusions: In summary, our results of this meta-analysis indicated that MMP-1(-1607)1G/2G polymorphism was significantly associated with cancer progress overall and 2G allele at the MMP-1 promoter region could be seen as a risk factor of cancer invasion and metastasis.