The effect of functional MAPKAPK2 copy number variation CNV-30450 on elevating nasopharyngeal carcinoma risk is modulated by EBV infection.
The effect of functional MAPKAPK2 copy number variation CNV-30450 on elevating nasopharyngeal carcinoma risk is modulated by EBV infection.
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DOI：
10.1093/carcin/bgt314
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发表时间：
2014
期刊：
影响因子：
4.7
通讯作者：
Lei Yang;B. Liu;Fuman Qiu;Binfang Huang;Yinyan Li;Dongsheng Huang;Rongrong Yang;Xiaorong Yang;Jieqiong Deng;Q. Jiang;Yifeng Zhou;Jiachun Lu
中科院分区：
文献类型：
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作者：
Lei Yang;B. Liu;Fuman Qiu;Binfang Huang;Yinyan Li;Dongsheng Huang;Rongrong Yang;Xiaorong Yang;Jieqiong Deng;Q. Jiang;Yifeng Zhou;Jiachun Lu
未标记的丝裂原活化蛋白激酶活化蛋白激酶2（MAPKAPK 2）在包括鼻咽癌（NPC）在内的癌症中的异常表达被认为是致癌的和在肿瘤发生中的模拟作用。我们假设复制MAPKAPK 2启动子的拷贝数变异（CNV）-30450可能影响MAPKAPK 2的表达，并与鼻咽癌风险相关。在中国南方和东部两个独立的病例对照组中，共1590名NPC患者和1979名无癌对照，我们通过TaqMan检测CNV-30450基因分型来研究CNV-30450与NPC风险的关系，并测试其生物学效应。在两个人群中观察到一致的发现，CNV-30450拷贝数增加与NPC风险增加相关（3/4拷贝vs 2拷贝：比值比= 1.28，95%置信区间= 1.10-1.49），其中存在不利基因型增强MAPKAPK 2启动子活性和升高MAPKAPK 2表达的生物学机制。CNV-30450基因型与EB病毒（EBV）感染在鼻咽癌发病中的交互作用显著（P = 0.035），且仅在EBV阳性病例中基因型与表型相关（P = 0.037），而在EBV阴性病例中无相关性（P = 0.366）。这些数据表明，MAPKAPK 2启动子中的功能性CNV-30450通过EBV感染的调节提高了NPC风险，这可能是NPC易感性的指标。这项病例对照研究表明，MAPKAPK 2启动子中的功能性CNV-30450通过EBV感染的调节提高了NPC的风险，这可能是NPC易感性的指标。
UNLABELLED Mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK2) is recognized as oncogenic and simulative role on tumorigenesis by virtue of abnormal expression in cancer including nasopharyngeal carcinoma (NPC). We hypothesized that the copy number variation (CNV)-30450, which duplicates the MAPKAPK2 promoter, may affect MAPKAPK2 expression and be associated with NPC risk. In two independent case-control panels of southern and eastern Chinese with a total of 1590 NPC patients and 1979 cancer-free controls, we investigated the association between CNV-30450 and NPC risk by genotyping the CNV-30450 with the TaqMan assay, and tested its biological effect. Consistent findings were observed in the two populations, that the increased copy number of CNV-30450 was associated with increased risk of NPC (3/4-copy versus 2-copy: odds ratio = 1.28, 95% confidence interval = 1.10-1.49), in which lies a biological mechanism that the adverse genotypes enhanced the promoter activity of MAPKAPK2 and elevated MAPKAPK2 expression. Moreover, the CNV-30450 adverse genotypes significantly interacted with Epstein-Barr virus (EBV) infection on increasing NPC risk (P = 0.035), and the genotype-phenotype correlation was only significant in EBV-positive cases (P = 0.037) but not in EBV-negative ones (P = 0.366). These data suggest that the functional CNV-30450 in the MAPKAPK2 promoter elevates the NPC risk with a modulation by EBV infection, which may be an indicator of susceptibility to NPC. SUMMARY This case-control study suggests that the functional CNV-30450 in the MAPKAPK2 promoter elevates the NPC risk with a modulation by EBV infection, which may be an indicator of susceptibility to NPC.