Tao Liu, Li Zuo, Lin Li, Lei Yin, Hongyuan Yu, Hongwei Jing, Yang Liu, Chuize Kong
1 Department of Urology, The First Hospital of China Medical University , Shenyang, People's Republic of China .
2 Department of Urology, The Second People's Hospital of Nanjing Medical University , Changzhou, People's Republic of China .
Genet Test Mol Biomarkers. 2015 Oct;19(10):548-55. doi: 10.1089/gtmb.2015.0123. Epub 2015 Aug 24.
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.
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.
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, pheterogeneity = 0.001) and renal cell carcinoma (2G1G vs. 1G1G: OR = 0.57, 95% CI = 0.39-0.82, pheterogeneity = 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, pheterogeneity = 0.195). For the MMP7 -181 A/G polymorphism, a decreased bladder cancer risk was found (G-allele vs. A-allele: OR = 0.81, 95% CI = 0.66-0.98, pheterogeneity =0.325).
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.
基质金属蛋白酶(MMPs)是一类高度保守的、依赖金属的蛋白水解酶家族,在肿瘤侵袭和转移中起重要作用。关于基质金属蛋白酶1(MMP1)、基质金属蛋白酶2(MMP2)、基质金属蛋白酶3(MMP3)、基质金属蛋白酶7(MMP7)和基质金属蛋白酶9(MMP9)基因多态性与尿路上皮癌风险之间的关联,已经开展了许多研究。然而,这些已发表研究的数据相互矛盾,且统计效力较低。
在本研究中,我们对截至2015年5月在PubMed和万方数据库中发表的12篇不同文献进行了荟萃分析,以更好地评估所声称的关联。计算优势比(OR)和95%置信区间(CI)以揭示关联强度。
发现了一些显著关联。对于MMP1 -1607 1G/2G多态性,在膀胱癌中,2G等位基因存在负向关联(2G2G + 2G1G vs. 1G1G:OR = 0.57,95% CI = 0.36 - 0.93,异质性p = 0.001),在肾细胞癌中也存在负向关联(2G1G vs. 1G1G:OR = 0.57,95% CI = 0.39 - 0.82,异质性p = 0.567)。对于MMP2 -1306 C/T多态性,在亚洲人群的膀胱癌中,T等位基因存在负向关联(TT + TC vs. CC:OR = 0.41,95% CI = 0.18 - 0.94,异质性p = 0.195)。对于MMP7 -181 A/G多态性,发现膀胱癌风险降低(G等位基因vs. A等位基因:OR = 0.81,95% CI = 0.66 - 0.98,异质性p = 0.325)。
总之,我们的研究表明,MMP1基因多态性在所有人群中,而MMP2和MMP7基因多态性仅在亚洲人群中,可能对膀胱癌风险具有保护作用。有必要开展样本量更大的未来研究,以更详细地进一步评估这些关联。