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A single nucleotide polymorphism in the Epstein-Barr virus genome is strongly associated with a high risk of nasopharyngeal carcinoma

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癌症 2015年第12期34卷 563-572页

作者： Fu-Tuo Feng Qian Cui Wen-Sheng Liu Yun-Miao Guo Qi-Sheng Feng Li-Zhen Chen Miao Xu Bing Luo Da-Jiang Li Li-Fu Hu Jaap M.Middeldorp octavia ramayanti Qian Tao Su-Mei Cao Wei-Hua Jia Jin-Xin Bei Yi-Xin Zeng Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer Medicine Department of Pathology VU University Medical Center Department of Medical Microbiology Qingdao University Medical College Department of Experimental Research Sun Yat-sen University Cancer Center Department of Microbiology Tumor and Cell BiologyKarolinska Institute Department of Clinical Oncology The Chinese University of Hong Kong Department of Epidemiology Cancer Prevention CenterSun Yat-sen University Cancer Center

Background:Epstein-Barr virus(EBV) commonly infects the general population and has been associated with nasopharyngeal carcinoma(NPC),which has a high incidence in certain *** study aimed to address how EBV variations contribute to the risk of ***:Using logistic regression analysis and based on the sequence variations at EBV-encoded RPMS1,a multistage association study was conducted to identify EBV variations associated with NPC risk.A protein degradation assay was performed to characterize the functional relevance of the RPMS1 ***:Based on EBV-encoded RPMS1 variations,a single nucleotide polymorphism(SNP) in the EBV genome(locus 155391:G>A,named Gl 55391 A) was associated with NPC in 157 cases and 319 healthy controls from an NPC endemic region in South China[P < 0.001,odds ratio(OR) = 4.47,95%confidence interval(CI) 2.71-7.37].The results were further validated in three independent cohorts from the NPC endemic region(P < 0.001,OR = 5.20,95%CI3.18-8.50 in 168 cases vs.241 controls,and P < 0.001,OR = 5.27,95%CI 4.06-6.85 in 726 cases vs.880 controls) and a non-endemic region(P < 0.001,OR = 7.52,95%CI 3.69-15.32 in 58 cases vs.612 controls).The combined analysis in 1109 cases and 2052 controls revealed that the SNP Gl 55391 A was strongly associated with NPC(P< 0.001,OR = 5.27,95%CI 4.31-6.44).Moreover,the frequency of the SNP Gl 55391 A was associated with NPC incidence but was not associated with the incidences of other EBV-related ***,the protein degradation assay showed that this SNP decreased the degradation of the oncogenic RPMS1 ***:Our study identified an EBV variation specifically and significantly associated with a high risk of *** findings provide insights into the pathogenesis of NPC and strategies for prevention.

关键词： Epstein-Barr virus Nasopharyngeal carcinoma RPMS1 Association

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