Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Cancer. 2011 Nov 15;117(22):5172-81. doi: 10.1002/cncr.26154. Epub 2011 Apr 26.
Matrix metalloproteinase-1 (MMP-1), an interstitial collagenase, plays an important role in the breakdown of extracellular matrix and mediates pathways of apoptosis, angiogenesis, and immunity. It has been demonstrated that the overexpression of this enzyme is associated with tumor initiation, invasion, and metastasis. The -1607 single guanine (1G)-to-2G polymorphism (reference single nucleotide polymorphism 1799750) in the MMP-1 promoter region creates an E26 (Ets) binding site and results in transcriptional up-regulation. The authors hypothesized that this MMP-1 polymorphism may affect susceptibility to the development and progression of cancer.
The authors investigated their hypothesis in a lung cancer case-control study. Genotypes were analyzed in 825 patients with lung cancer and in 825 controls. Odds ratios were estimated by multivariate logistic regression, and a meta-analysis also was conducted to verify the findings.
Patients who had the MMP-1 2G/2G genotype had a 1.71-fold increased risk of lung cancer (95% confidence interval, 1.22-fold to 2.41-fold increased risk) compared with patients who had the 1G/1G genotype. Moreover, when patients with stage I disease were considered as a reference group, patients who carried the 2G/2G genotype had a significantly increased risk of invasive disease (stage III-IV: odds ratio, 2.02; 95% confidence interval, 1.09-3.74) compared with patients who had the 1G/1G genotype. Pooled results from the meta-analysis confirmed that those who had the 2G/2G genotype had a significantly increased risk of lung cancer compared with those who had the 1G/1G genotype, consistent with the case-control findings.
The current study demonstrated that the MMP-1 -1607 1G-to-2G polymorphism is associated with susceptibility to both development and progression of lung cancer.
基质金属蛋白酶-1（MMP-1），一种间质胶原酶，在细胞外基质的分解和凋亡、血管生成和免疫途径的调节中发挥重要作用。已经证明，这种酶的过度表达与肿瘤的发生、浸润和转移有关。MMP-1 启动子区域的-1607 位单核苷酸鸟嘌呤（1G）到 2G 多态性（参考单核苷酸多态性 1799750）创建了一个 E26（Ets）结合位点，并导致转录上调。作者假设这种 MMP-1 多态性可能影响癌症发生和发展的易感性。
作者在一项肺癌病例对照研究中研究了他们的假设。在 825 例肺癌患者和 825 例对照中分析了基因型。通过多变量逻辑回归估计比值比，并进行荟萃分析以验证研究结果。
与 1G/1G 基因型的患者相比，MMP-1 2G/2G 基因型的患者患肺癌的风险增加了 1.71 倍（95%置信区间，1.22 倍至 2.41 倍）。此外，当将 I 期疾病患者作为参考组时，携带 2G/2G 基因型的患者发生侵袭性疾病的风险显著增加（III-IV 期：比值比，2.02；95%置信区间，1.09-3.74）与 1G/1G 基因型的患者相比。荟萃分析的汇总结果证实，与 1G/1G 基因型的患者相比，2G/2G 基因型的患者患肺癌的风险显著增加，与病例对照研究结果一致。
本研究表明，MMP-1-1607 1G 到 2G 多态性与肺癌的发生和发展易感性相关。
