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MCP-1 启动子多态性与鼻咽癌易感性的关联。

Association of MCP-1 promoter polymorphism with susceptibility to nasopharyngeal carcinoma.

机构信息

Department of Genomics & Proteomics, State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China.

ENT Department, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China.

出版信息

J Cell Biochem. 2019 Apr;120(4):6661-6670. doi: 10.1002/jcb.27962. Epub 2018 Oct 28.

Abstract

Nasopharyngeal carcinoma (NPC) is prevalent among populations from southern China and is influenced by both genetic and environmental risk factors. The monocyte chemoattractant protein-1 (MCP-1), a member of cysteine-cysteine chemokine family, plays critical roles in cancers. A polymorphism within the MCP-1 promoter, rs1024611, has been shown to be significantly associated with the risk of several cancers. Our purpose was to assess the role of rs1024611 in NPC susceptibility. By polymerase chain reaction-restriction fragment length polymorphism method, we genotyped rs1024611 in 593 patients with NPC (cases) and 480 cancer-free subjects (controls) among Guangxi population from southern China. We observed that the G allele of rs1024611 was significantly associated with the increased risk of NPC in an additive model and dominant model, respectively (P = 0.018 and 0.010, odds ratio = 1.25 and 1.41, respectively). No appreciable variation of the effects was found across the subgroups stratified by age, sex, nationality, smoking and drinking status, and smoking level. In addition, significantly higher messenger RNA (mRNA) expression level of MCP-1 was observed in NPC tissues than that in normal nasopharyngeal tissues, and the G allele of rs1024611 was significantly associated with elevated mRNA expression level of MCP-1 in Epstein-Barr virus-transformed lymphocytes. In conclusion, our findings suggested that rs1024611 at the MCP-1 promoter may be a risk factor for NPC. Further studies with larger sample size are necessary to confirm these findings.

摘要

鼻咽癌(NPC)在中国南方人群中较为常见,受遗传和环境风险因素的影响。单核细胞趋化蛋白-1(MCP-1)是半胱氨酸-半胱氨酸趋化因子家族的一员,在癌症中发挥着关键作用。MCP-1 启动子内的一个多态性,rs1024611,已被证明与几种癌症的风险显著相关。我们的目的是评估 rs1024611 在 NPC 易感性中的作用。通过聚合酶链反应-限制性片段长度多态性方法,我们对来自中国南方广西人群的 593 名 NPC 患者(病例)和 480 名无癌症对照(对照)进行了 rs1024611 基因分型。我们观察到 rs1024611 的 G 等位基因分别在加性模型和显性模型中与 NPC 的风险增加显著相关(P=0.018 和 0.010,优势比=1.25 和 1.41)。在按年龄、性别、国籍、吸烟和饮酒状况以及吸烟水平分层的亚组中,未发现作用的明显变化。此外,与正常鼻咽组织相比,NPC 组织中 MCP-1 的信使 RNA(mRNA)表达水平明显升高,rs1024611 的 G 等位基因与 EBV 转化的淋巴细胞中 MCP-1 的 mRNA 表达水平升高显著相关。总之,我们的研究结果表明,MCP-1 启动子上的 rs1024611 可能是 NPC 的一个危险因素。需要更大样本量的进一步研究来证实这些发现。

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