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

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

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

Author: Fu-Tuo FENG ^{1
,

2} ; Qian CUI ³ ; Wen-Sheng LIU ⁴ ; Yun-Miao GUO ⁵ ; Qi-Sheng FENG ⁶ ; Li-Zhen CHEN ⁷ ; Miao XU ⁸ ; Bing LUO ^{2
,

9} ; Da-Jiang LI ¹⁰ ; Li-Fu HU ¹¹ ; Jaap M MIDDELDORP ¹² ; Octavia RAMAYANTI ¹³ ; Qian TAO ¹⁴ ; Su-Mei CAO ¹⁵ ; Wei-Hua JIA ¹⁶ ; Jin-Xin BEI ¹⁷ ; Yi-Xin ZENG ¹⁸
Author Information

1. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China. futuo_feng@
2. com.
3. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China. cuiqian@sysucc.org.cn.
4. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China. liuwsh@sysucc.org.cn.
5. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China. guoym@sysucc.org.cn.
6. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China. fengqsh@sysucc.org.cn.
7. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China. chenlizh@sysucc.org.cn.
8. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China. xumiao@sysucc.org.cn.
9. Department of Medical Microbiology, Qingdao University Medical College, Qingdao, 266021, Shandong, P. R. China. qdluobing@
10. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China. dajiang.li@hsc.utah.edu.
11. Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177, Stockholm, Sweden. Lifu.Hu@ki.se.
12. Department of Pathology, VU University Medical Center, Amsterdam, 1007 MB, The Netherlands. j.middeldorp@vumc.nl.
13. Department of Pathology, VU University Medical Center, Amsterdam, 1007 MB, The Netherlands. o.ramayanti@vumc.nl.
14. Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong, 999077, P. R. China. qtao@cuhk.edu.hk.
15. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China. caosm@sysucc.org.cn.
16. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China. jiaweih@mail.sysu.edu.cn.
17. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China. beijx@sysucc.org.cn.
18. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China. zengyx@sysucc.org.cn.
Publication Type:Journal Article
MeSH: Adult; Aged; Carcinoma; Case-Control Studies; China; epidemiology; Epstein-Barr Virus Infections; complications; epidemiology; virology; Female; Genetic Association Studies; Genome, Viral; Herpesvirus 4, Human; genetics; isolation & purification; Humans; Incidence; Male; Middle Aged; Nasopharyngeal Neoplasms; epidemiology; virology; Neoplasm Proteins; genetics; Pilot Projects; Polymorphism, Single Nucleotide; Risk Assessment; methods; Tumor Cells, Cultured; Viral Proteins; genetics
From:Chinese Journal of Cancer 2015;34(12):563-572
CountryChina
Language:English
Abstract:
BACKGROUNDEpstein-Barr virus (EBV) commonly infects the general population and has been associated with nasopharyngeal carcinoma (NPC), which has a high incidence in certain regions. This study aimed to address how EBV variations contribute to the risk of NPC.
METHODSUsing logistic regression analysis and based on the sequence variations at EBV-encoded RPMS1, a multi-stage 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 variations.
RESULTSBased on EBV-encoded RPMS1 variations, a single nucleotide polymorphism (SNP) in the EBV genome (locus 155391: G>A, named G155391A) 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% CI 3.18-8.50 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 G155391A was strongly associated with NPC (P(combined) < 0.001, OR = 5.27, 95% CI 4.31-6.44). Moreover, the frequency of the SNP G155391A was associated with NPC incidence but was not associated with the incidences of other EBV-related malignancies. Furthermore, the protein degradation assay showed that this SNP decreased the degradation of the oncogenic RPMS1 protein.
CONCLUSIONSOur study identified an EBV variation specifically and significantly associated with a high risk of NPC. These findings provide insights into the pathogenesis of NPC and strategies for prevention.