Background Epstein-Barr virus （EBV） commonly infects the general population and has been associated withnasopharyngeal carcinoma （NPC）, which has a high incidence in certain regions.This study aimed to address how...Background Epstein-Barr virus （EBV） commonly infects the general population and has been associated withnasopharyngeal carcinoma （NPC）, which has a high incidence in certain regions.This study aimed to address how EBVvariations contribute to the risk of NPC.Methods： Using logistic regression analysis and based on the sequence variations at EBV-encoded RPMSh a multistageassociation study was conducted to identify EBV variations associated with NPC risk. A protein degradationassay was performed to characterize the functional relevance of the RPMS1 variations.Results： Based on EBV-encoded RPMS1 variations, a single nucleotide polymorphism （SNP） in the EBV genome（locus 155391： G〉A, named G155391 A） was associated with NPC in 157 cases and 319 healthy controls from an NPCendemic region in South China [P 〈 0.001, odds ratio （OR） = 4.47,95% confidence interval （Cl） 2.71-7.37].The resultswere further validated in three independent cohorts from the NPC endemic region （P 〈 0.001, OR = 5.20,95% Cl3.18-8.50 in 168 cases vs. 241 controls, and P 〈 0.001, OR = 5.27,95% Cl 4.06-6.85 in 726 cases vs. 880 controls） anda non-endemic region （P 〈 0.001, OR = 7.52,95% Cl 3.69-1532 in 58 cases vs. 612 controls）.The combined analysisin 1109 cases and 2052 controls revealed that the SNP G155391A was strongly associated with NPC （Pcomb/ned 〈 0.001,OR = 5.27,95% Cl 4.31-6.44）. Moreover, the frequency of the SNP G155391A was associated with NPC incidence butwas not associated with the incidences of other EBV-related malignancies. Furthermore, the protein degradation assayshowed that this SNP decreased the degradation of the oncogenic RPMS1 protein.Conclusions： Our study identified an EBV variation specifically and significantly associated with a high risk of NPCThese findings provide insights into the pathogenesis of NPC and strategies for prevention.展开更多
文摘Background Epstein-Barr virus （EBV） commonly infects the general population and has been associated withnasopharyngeal carcinoma （NPC）, which has a high incidence in certain regions.This study aimed to address how EBVvariations contribute to the risk of NPC.Methods： Using logistic regression analysis and based on the sequence variations at EBV-encoded RPMSh a multistageassociation study was conducted to identify EBV variations associated with NPC risk. A protein degradationassay was performed to characterize the functional relevance of the RPMS1 variations.Results： Based on EBV-encoded RPMS1 variations, a single nucleotide polymorphism （SNP） in the EBV genome（locus 155391： G〉A, named G155391 A） was associated with NPC in 157 cases and 319 healthy controls from an NPCendemic region in South China [P 〈 0.001, odds ratio （OR） = 4.47,95% confidence interval （Cl） 2.71-7.37].The resultswere further validated in three independent cohorts from the NPC endemic region （P 〈 0.001, OR = 5.20,95% Cl3.18-8.50 in 168 cases vs. 241 controls, and P 〈 0.001, OR = 5.27,95% Cl 4.06-6.85 in 726 cases vs. 880 controls） anda non-endemic region （P 〈 0.001, OR = 7.52,95% Cl 3.69-1532 in 58 cases vs. 612 controls）.The combined analysisin 1109 cases and 2052 controls revealed that the SNP G155391A was strongly associated with NPC （Pcomb/ned 〈 0.001,OR = 5.27,95% Cl 4.31-6.44）. Moreover, the frequency of the SNP G155391A was associated with NPC incidence butwas not associated with the incidences of other EBV-related malignancies. Furthermore, the protein degradation assayshowed that this SNP decreased the degradation of the oncogenic RPMS1 protein.Conclusions： Our study identified an EBV variation specifically and significantly associated with a high risk of NPCThese findings provide insights into the pathogenesis of NPC and strategies for prevention.
