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白细胞介素-8(-251)T/A基因多态性与鼻咽癌易感性及侵袭性的关联

Association of IL-8 (-251)T/A polymorphism with susceptibility to and aggressiveness of nasopharyngeal carcinoma.

作者信息

Ben Nasr Hela, Chahed Karim, Mestiri Souhir, Bouaouina Noureddine, Snoussi Kaouther, Chouchane Lotfi

机构信息

Laboratoire d'Immuno-Oncologie Moléculaire, Faculté de Médecine de Monastir, Monastir, Tunisia.

出版信息

Hum Immunol. 2007 Sep;68(9):761-9. doi: 10.1016/j.humimm.2007.06.006. Epub 2007 Jul 18.

DOI:10.1016/j.humimm.2007.06.006
PMID:17869651
Abstract

Interleukin-8 (IL-8) is an angiogenic chemokine that plays a potent role in both development and progression of many human malignancies including nasopharyngeal carcinoma (NPC). In the present study, we evaluated the susceptibility and prognostic implications of the (-251) T/A genetic variation in IL-8 in NPC. We used the allele-specific polymerase chain reaction to characterize the variation of the IL-8 promoter region for 160 unrelated Tunisian patients with NPC and 169 healthy control subjects. There was a significant association between the homozygotes IL-8 (-251) AA genotype and nasopharyngeal carcinoma (OR = 2.46; P = 0.004). The presence of the IL-8 (-251) AA genotype was highly associated with elevated NPC risk for male patients. A significant association was demonstrated between the IL-8 (-251) AA genotype and the aggressive forms of NPC as defined by large tumor size, lymph node metastasis, and advanced stages. Moreover, the presence of the IL-8 (-251) AA genotype indicated a significant association with decreased overall survival. Our findings suggest that the IL-8 promoter polymorphism is associated with increased nasopharyngeal carcinoma risk, particularly in males, as well as disease progress, supporting our hypothesis for IL-8 involvement in NPC pathogenesis.

摘要

白细胞介素-8(IL-8)是一种血管生成趋化因子,在包括鼻咽癌(NPC)在内的许多人类恶性肿瘤的发生和发展中都发挥着重要作用。在本研究中,我们评估了NPC患者中IL-8基因(-251)T/A遗传变异的易感性及其预后意义。我们采用等位基因特异性聚合酶链反应,对160例无亲缘关系的突尼斯NPC患者和169例健康对照者的IL-8启动子区域变异进行了分析。纯合子IL-8(-251)AA基因型与鼻咽癌之间存在显著关联(比值比=2.46;P=0.004)。IL-8(-251)AA基因型的存在与男性患者患NPC的风险升高高度相关。IL-8(-251)AA基因型与肿瘤体积大、有淋巴结转移及晚期等侵袭性形式的NPC之间存在显著关联。此外,IL-8(-251)AA基因型的存在表明与总生存率降低显著相关。我们的研究结果表明,IL-8启动子多态性与鼻咽癌风险增加相关,尤其是在男性中,并且与疾病进展有关,这支持了我们关于IL-8参与NPC发病机制的假设。

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