Functional polymorphism in the 5'-UTR of CR2 is associated with susceptibility to nasopharyngeal carcinoma.

Functional polymorphism in the 5'-UTR of CR2 is associated with susceptibility to nasopharyngeal carcinoma.
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DOI:
10.3892/or.2013.2421
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发表时间:
2013-07
期刊:
影响因子:
4.2
通讯作者:
Jia WH
Jia WH
中科院分区:
医学3区
文献类型:
--
作者:
Fan Q;He JF;Wang QR;Cai HB;Sun XG;Zhou XX;Qin HD;Shugart YY;Jia WH

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eb病毒(EBV)相关鼻咽癌(NPC)是中国南部和东南亚地区的一种地方性鳞状细胞癌。研究表明,EBV感染期间的炎症和免疫反应有助于鼻咽癌的发展。补体受体2 (CR2)基因在炎症和免疫反应中起核心作用,因此是鼻咽癌的一个很好的候选易感基因。我们利用pcr测序技术鉴定了广东人CR2基因外显子区域的多个单核苷酸多态性(SNPs)。从528例鼻咽癌患者和408例正常人中筛选出2个snp,根据年龄、性别和居住地进行匹配的病例对照研究。此外,我们将整个5 ' -UTR和整个CR2启动子克隆到荧光素酶报告系统中,并比较了不同等位基因结构之间的荧光素酶活性。CR2 5′-UTR SNP (24 T/C, rs3813946)与广东人群鼻咽癌有显著相关性(P<0.01)。将受试者分为年龄≤45岁组1和年龄≤45岁组2。1组患者24 T/C等位基因频率与对照组比较差异有统计学意义(P=0.0034)。比值比(OR=1.81)也表明携带次要等位基因c的个体患NPC的风险更高。所有等位基因对荧光素酶活性都有影响,但只有易感等位基因+24C结构的活性增加。我们的研究结果提示CR2是鼻咽癌的易感基因,并提示CR2表达的增强可能参与鼻咽癌的发生和发展。
Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is a squamous cell cancer endemic in Southern China and Southeast Asia. It has been shown that inflammatory and immune responses during EBV infection contribute to the development of NPC. The complement receptor 2 (CR2) gene plays central roles during inflammatory and immune responses and, therefore, is a good candidate susceptibility gene for NPC. We performed PCR-based sequencing to identify multiple single-nucleotide polymorphisms (SNPs) within the exon regions of the CR2 gene in a Cantonese population. Two SNPs were screened in 528 NPC patients and 408 normal individuals to perform a case-control study matched according to age, gender and residence. Furthermore, we cloned the entire 5′-UTR and entire CR2 promoter into a luciferase report system and compared the luciferase activities between the different allelic constructs. A SNP in the 5′-UTR of CR2 (24 T/C, rs3813946) showed a significant association (P<0.01) with NPC in the Cantonese population studied. The subjects were categorized into 2 age groups: group 1, age ≤45 years and group 2, age >45 years. In group 1, the allelic frequencies of 24 T/C in the patients were significantly different from those of the controls (P=0.0034). The odds ratio (OR=1.81) also indicated a higher risk of NPC in individuals who carried the minor allele C. All constructs exerted allelic differences on luciferase activities, but only the susceptible allele +24C construct showed increased activity. Our findings implicate CR2 as a susceptibility gene for NPC and suggest that enhanced CR2 expression may be involved in the oncogenesis and development of NPC.
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