Association between polymorphisms in the promoter regions of matrix metalloproteinases (MMPs) and risk of cancer metastasis: a meta-analysis

Abstract

Background: A variety of studies have evaluated the associations between polymorphisms in the promoter regions of Matrix metalloproteinases (MMPs) and cancer metastasis. However, the results remain inconclusive. To better understand the roles of MMP polymorphisms in metastasis, we conducted a comprehensive meta-analysis.

Methods: Electronic databases were searched (from January 2000 to June 2011) for any MMP genetic association studies in metastasis. Overall and subgroup analyses were performed. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the associations between MMP polymorphisms and metastasis. Statistical analysis was performed with Review Manager 5.0 and STATA11.0.

Results: Thirty-three studies addressing five MMP polymorphisms were analyzed among 10,516 cancer cases (4,059 metastasis-positive cases and 6,457 metastasis-negative cases). For MMP1 (-1607)1G/2G, genotype 2G/2G increased the overall risk of metastasis under the recessive model (OR = 1.44, 95% CI = 1.05-1.98). In subgroup analysis based on cancer type, associations were found in head/neck and breast cancer under the recessive model, and also in breast cancer under the dominant model. For MMP3 (-1171) 5A/6A, the polymorphism decreased the overall risk of metastasis under two genetic models (recessive: OR = 0.80, 95%CI = 0.64-0.99, dominant: OR = 0.72, 95%CI = 0.56-0.93). The polymorphisms of MMP7 (-181) A/G and MMP9 (-1562) C/T increased metastatic risk. However, no association was observed between MMP2 (-1306) C/T and metastasis.

Conclusions: Our investigations demonstrate that polymorphisms in the promoter regions of MMP1, 3, 7 and 9 might be associated with metastasis in some cancers. Further studies with large sample size for MMP2 should be conducted.

Figure 1. Flow diagram of study identification.

Figure 2. Forest plot of cancer metastasis risk associated with MMP1 (−1607) 1G>2G under the recessive model.

A random-effects model was used. The squares and horizontal line represent the study-specific OR and 95% CI. The diamond represents the pooled results of OR and 95% CI.

Figure 3. Forest plot of cancer metastasis risk associated with MMP3 (−1171) 5A>6A.

A fixed-effects model was used. A indicates the result under the dominant model (6A/6A+5A/6A vs. 5A/5A). B indicates the result under the recessive model (6A/6A vs. 5A/5A+5A/6A). The squares and horizontal line represent the study-specific OR and 95% CI. The diamond represents the pooled results of OR and 95% CI.

Figure 4. Forest plot of cancer metastasis risk associated with MMP9 (−1562) C>T under the dominant model.

A fixed-effects model was used. The squares and horizontal line represent the study-specific OR and 95% CI. The diamond represents the pooled results of OR and 95% CI.

Figure 5. Forest plot of cancer metastasis risk associated with MMP7 (−181) A>G.

A fixed-effects model was used. A indicates the result under the dominant model (GG+AG vs. AA). B indicates the result under the recessive model (GG vs. AG+AA). The squares and horizontal line represent the study-specific OR and 95% CI. The diamond represents the pooled results of OR and 95% CI.