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PTGS2(环氧化酶-2)-765 G>C功能性启动子多态性及其与鼻咽癌风险和淋巴结转移的关联

PTGS2 (COX-2) -765 G > C functional promoter polymorphism and its association with risk and lymph node metastasis in nasopharyngeal carcinoma.

作者信息

Ben Nasr Hela, Chahed Karim, Bouaouina Noureddine, Chouchane Lotfi

机构信息

Faculté de Médecine de Monastir, Université de Monastir, Monastir, 5019, Tunisia.

出版信息

Mol Biol Rep. 2009 Jan;36(1):193-200. doi: 10.1007/s11033-007-9166-3. Epub 2007 Oct 30.

Abstract

Cyclooxygenase-2 (Cox-2) is a key enzyme in the conversion of arachidonic acid to prostaglandins that has been shown to have a particular importance in the progression of several malignancies including nasopharyngeal carcinoma (NPC). In the current report, we designed a case-controlled study to evaluate the susceptibility and prognostic implications of the functional -765 G > C genetic variation in NPC. A PCR and restriction fragment length polymorphism analysis was used to determine the polymorphism in a Tunisian population of patients with NPC (n = 180) and in healthy control subjects (n = 169). A higher risk for NPC was observed for carriers of COX-2 -765 C allele (OR = 1.76; P = 0.01). This association remains significant after adjustments for age and sex (OR = 1.89; P = 0.008). Regarding prognostic indicators, a significant association was found between -765 C allele carriers and the presence of lymph node metastasis (OR = 2.28; P = 0.01), as well as, with tumor stage (OR = 2.73; P = 0.03). This is the first report on the studies of COX-2 SNPs in NPC and our data suggest that this genetic variant may play a role in mediating susceptibility to NPC, as well as, in neoplastic progression, a finding which further supports the involvement of COX-2 in NPC etiology.

摘要

环氧化酶-2(Cox-2)是将花生四烯酸转化为前列腺素的关键酶,已证明其在包括鼻咽癌(NPC)在内的多种恶性肿瘤进展中具有特殊重要性。在本报告中,我们设计了一项病例对照研究,以评估NPC中功能性-765 G>C基因变异的易感性和预后意义。采用聚合酶链反应和限制性片段长度多态性分析来确定突尼斯NPC患者群体(n = 180)和健康对照者(n = 169)中的多态性。COX-2 -765 C等位基因携带者患NPC的风险更高(比值比= 1.76;P = 0.01)。在对年龄和性别进行调整后,这种关联仍然显著(比值比= 1.89;P = 0.008)。关于预后指标,发现-765 C等位基因携带者与淋巴结转移的存在(比值比= 2.28;P = 0.01)以及肿瘤分期(比值比= 2.73;P = 0.03)之间存在显著关联。这是关于NPC中COX-2单核苷酸多态性研究的首份报告,我们的数据表明这种基因变异可能在介导NPC易感性以及肿瘤进展中发挥作用,这一发现进一步支持了COX-2参与NPC病因学的观点。

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