A metalloproteinase-9 polymorphism which affects its expression is associated with increased risk for oral squamous cell carcinoma
A metalloproteinase-9 polymorphism which affects its expression is associated with increased risk for oral squamous cell carcinoma
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DOI：
10.1016/j.ejso.2007.03.024
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发表时间：
2008-04-01
期刊：
影响因子：
3.8
通讯作者：
Patsouris, E.
中科院分区：
文献类型：
--
作者：
Vairaktaris, E.;Vassiliou, S.;Patsouris, E.
目的：根据最近发现的与血管生成、血栓形成和炎症相关的因素对癌变的贡献，我们研究了金属蛋白酶-9（MMP-9）与口腔癌风险增加的可能关联。在152名口腔鳞状细胞癌患者和162名种族、年龄和性别相当的健康对照的DNA样本中，结果：MMP-9基因启动子区-1562 C/T多态性在患者组中的高表达T等位基因的检出率明显高于对照组（分别为22%和15%; P < 0.05）。这种差异是由于患者组与对照组相比C/T杂合子的相对增加（P < 0.05，95%OR1.92，CI1.21 -3.06）。同样的模式之间观察到的显着性控制和亚组的患者的初始（I & II）阶段的癌症，没有积极的癌症或血栓形成的家族史，吸烟和酗酒的habites.Conclusions：研究MMP-9的多态性有很强的关联，在一个子集的一般人群中发展口腔癌的风险增加。这些结果与以前的研究一致MMP-9在侵袭性口腔癌细胞系中的组成性表达和分泌。观察到T等位基因携带者仅在初始阶段而不是在晚期阶段具有发展口腔癌的增加的风险，这可能是由于MMP-9通过从纤溶酶原产生血管抑素而在抑制血管生成中的作用。(C)2007爱思唯尔有限公司保留所有权利。
Aim: In light to recently found contribution of factors associated with angiogenesis, thrombosis and inflammation to carcinogenesis, we investigated the possible association of metalloproteinase-9 (MMP-9) with increased risk of oral cancer.Methods: In DNA samples of 152 patients with oral squamous cell carcinoma and 162 healthy controls of comparable ethnicity, age and sex, we studied the -1562 C/T polymorphism in the MMP-9 gene promoter, which affects its transcription.Results: The detected frequency for the high expression T allele in the patients' group was significantly increased in comparison to that of the control group (22% versus 15%, respectively; P < 0.05). This difference was due to the relative increase of C/T heterozygotes in the group of patients, in comparison to controls (P < 0.05, 95% OR 1.92, CI 1.21-3.06). The same pattern of significance was observed between controls and the subgroups of patients with initial (I & II) stages of cancer, without positive family history of cancer or thrombophilia, with smoking and alcohol abuse habits.Conclusions: The investigated MMP-9 polymorphism has a strong association with increased risk for developing oral cancer in a subset of the general population. These results are in accordance to previous studies of constitutive expression and secretion of MMP-9 in invasive oral carcinoma cell lines. The observation that T allele carriers have an increased risk for developing oral cancer only in initial stages, but not in advanced ones, may be due to the role of MMP-9 in the inhibition of angiogenesis by generating angiostatin from plasminogen. (C) 2007 Elsevier Ltd. All rights reserved.