新加坡人类遗传与基因组组研究所的Jianjun Liu和中国中山大学肿瘤中心Yi-Xin Zeng课题组合作，用基因组测序分析确定了与鼻咽癌高风险相关的人类疱疹病毒第四型(EBV,也译作爱泼斯坦-巴尔病毒)。 该研究于2019年7月发表于国际学术期刊《自然—遗传学》。

研究人员基于对270株EBV分离株的大规模基因组测序结果和中国对EBV分离株的两阶段关联研究，他们在BALF2中发现了两个与鼻咽癌风险密切相关的非同义EBV变异(SNP 162476_C的优势比(OR) = 8.69, P = 9.69×10⁻²⁵;对于SNP 163364_T, OR = 6.14, P = 2.40×10 ^{- 32})。这些变异的累积效应占华南地区鼻咽癌总风险的83%。对这些危险变异的系统发育分析显示，它们在亚洲具有独特的起源，随后在鼻咽癌流行地区克隆扩增。研究结果为中国南方鼻咽癌的流行提供了新的视角，同时也为鼻咽癌的预防提供了高危人群的识别。

据介绍，人类疱疹病毒第四型(EBV)感染在世界范围内普遍存在，并与包括鼻咽癌(NPC)在内的多种癌症有关。EBV病毒基因组变异在鼻咽癌发生发展中的重要性及其在华南地区的显著流行尚未得到充分的研究。

附：英文原文

Title: Genome sequencing analysis identifies Epstein-Barr virus subtypes associated with high risk of nasopharyngeal carcinoma

Author: Miao Xu, Youyuan Yao, Hui Chen, Shanshan Zhang, Su-Mei Cao, Zhe Zhang, Bing Luo, Zhiwei Liu, Zilin Li, Tong Xiang, Guiping He, Qi-Sheng Feng, Li-Zhen Chen, Xiang Guo, Wei-Hua Jia, Ming-Yuan Chen, Xiao Zhang, Shang-Hang Xie, Roujun Peng, Ellen T. Chang, Vincent Pedergnana, Lin Feng, Jin-Xin Bei, Rui-Hua Xu, Mu-Sheng Zeng, Weimin Ye, Hans-Olov Adami, Xihong Lin, Weiwei Zhai, Yi-Xin Zeng, Jianjun Liu

Issue&Volume: Volume 51 Issue 7, July 2019

Abstract: Epstein–Barr virus (EBV) infection is ubiquitous worldwide and is associated with multiple cancers, including nasopharyngeal carcinoma (NPC). The importance of EBV viral genomic variation in NPC development and its striking epidemic in southern China has been poorly explored. Through large-scale genome sequencing of 270 EBV isolates and two-stage association study of EBV isolates from China, we identify two non-synonymous EBV variants within BALF2 that are strongly associated with the risk of NPC (odds ratio (OR)=8.69, P=9.69×1025 for SNP 162476_C; OR=6.14, P=2.40×1032 for SNP 163364_T). The cumulative effects of these variants contribute to 83% of the overall risk of NPC in southern China. Phylogenetic analysis of the risk variants reveals a unique origin in Asia, followed by clonal expansion in NPC-endemic regions. Our results provide novel insights into the NPC endemic in southern China and also enable the identification of high-risk individuals for NPC prevention.

DOI: 10.1038/s41588-019-0436-5

Source: https://www.nature.com/articles/s41588-019-0436-5