State Key Laboratory of Genetic Engineering, Department of Genetics, Institute of Genetics, School of Life Science, Fudan University, Shanghai, People's Republic of China.
Mutagenesis. 2010 Jul;25(4):371-9. doi: 10.1093/mutage/geq015. Epub 2010 Apr 1.
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.
基质金属蛋白酶（MMP）2、MMP7 和 MMP9 是 MMP 家族的重要成员。这些 MMP 启动子区域的四个多态性，即 MMP2-1306C>T、MMP2-735C>T、MMP7-181A>G 和 MMP9-1562C>T，已被报道具有功能，可能导致癌症的遗传易感性。然而，由于来自不同病例对照研究的结果相互矛盾，这些多态性与癌症风险之间的关联仍然没有定论。为了更好地评估这些多态性在癌症发展中的作用，我们进行了一项荟萃分析，该分析包括 51 项研究，超过 40000 名受试者。结果表明，在显性遗传模型下，MMP2-1306T 与肺癌[比值比（OR）=0.50，95%置信区间（CI）0.43-0.59，P（异质性）=0.147，I²=44.1%]、头颈部癌症（OR=0.53，95%CI 0.41-0.69，P（异质性）=0.974，I²=0.0%）和食管癌（OR=0.67，95%CI 0.55-0.80，P（异质性）=0.593，I²=0.0%）的易感性较低有关；MMP2-735T 与肺癌（OR=0.65，95%CI 0.53-0.79，P（异质性）=0.42，I²=0.0%）和食管癌（OR=0.84，95%CI 0.70-0.99，P（异质性）=0.206，I²=37.4%）的风险降低有关；MMP7-181AG 和 GG 基因型携带者患胃癌的风险增加（OR=1.90，95%CI 1.43-2.51，P（异质性）=0.992，I²=0.0%），而 MMP9-1562C>T 与全组分析（OR=0.99，95%CI 0.91-1.08，P（异质性）=0.419，I²=3.0%）和亚组分析中的癌症风险无关。总之，我们的荟萃分析表明，MMP2-1306C>T、MMP2-735C>T 和 MMP7-181A>G 可能在癌症发展中发挥等位基因特异性作用，而 MMP9-1562C>T 可能不是大多数癌症类型的主要危险因素。应该进行大规模的病例对照研究，以更详细地阐明这四个多态性在不同类型癌症中的可能作用。
