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Genome sequencing analysis identifies high-risk Epstein-Barr virus subtypes for nasopharyngeal carcinoma

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

Posted 04 Dec 2018
bioRxiv DOI: 10.1101/486613 (published DOI: 10.1038/s41588-019-0436-5)

Epstein-Barr virus (EBV) infection is ubiquitous worldwide and associated with multiple cancers including nasopharyngeal carcinoma (NPC). The role of EBV viral genomic variation in NPC development and its striking endemicity in southern China has been poorly explored. Through large-scale genome sequencing and association study of EBV isolates from China, we identified two non-synonymous EBV variants within BALF2 strongly associated with NPC risk (conditional P value 1.75 X 10-6 for SNP162476_C and 3.23 X 10-13 for SNP163364_T), whose cumulative effects contributed to 83% of the overall risk in southern China. Phylogenetic analysis of the risk variants revealed a unique origin in southern China followed by clonal expansion. EBV BALF2 haplotype carrying the risk variants were shown to reduce viral lytic DNA replication, as a result potentially promoting viral latency. Our discovery has not only provided insight to the unique endemic pattern of NPC occurrence in southern China, but also paved the way for the identification of individuals at high risk of NPC and effective intervention program to reduce the disease burden in southern China.

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