Department of Medical Genetics, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China.
PLoS One. 2012;7(2):e31251. doi: 10.1371/journal.pone.0031251. Epub 2012 Feb 14.
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.
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.
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.
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.
多项研究评估了基质金属蛋白酶（MMPs）启动子区域的多态性与癌症转移之间的关系。然而，结果仍不确定。为了更好地理解 MMP 多态性在转移中的作用，我们进行了一项综合荟萃分析。
从 2000 年 1 月至 2011 年 6 月，我们对任何 MMP 遗传关联研究的电子数据库进行了检索（转移中的 MMP 遗传关联研究）。进行了总体和亚组分析。比值比（OR）和 95%置信区间（CI）用于评估 MMP 多态性与转移之间的关系。统计分析使用 Review Manager 5.0 和 STATA11.0 进行。
分析了 10516 例癌症病例（4059 例转移阳性病例和 6457 例转移阴性病例）中的 33 项 MMP 多态性研究。对于 MMP1（-1607）1G/2G，在隐性模型下，基因型 2G/2G 增加了转移的总体风险（OR=1.44，95%CI=1.05-1.98）。在基于癌症类型的亚组分析中，在隐性模型下发现了头颈部和乳腺癌的相关性，在显性模型下也发现了乳腺癌的相关性。对于 MMP3（-1171）5A/6A，该多态性在两种遗传模型下降低了转移的总体风险（隐性：OR=0.80，95%CI=0.64-0.99，显性：OR=0.72，95%CI=0.56-0.93）。MMP7（-181）A/G 和 MMP9（-1562）C/T 的多态性增加了转移的风险。然而，MMP2（-1306）C/T 与转移之间没有关联。
我们的研究表明，MMP1、3、7 和 9 启动子区域的多态性可能与某些癌症的转移有关。对于 MMP2，应该进行具有更大样本量的进一步研究。
