Genome sequencing analysis identifies Epstein–Barr virus subtypes associated with high risk of nasopharyngeal carcinoma

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

doi:10.1038/s41588-019-0436-5

Genome sequencing analysis identifies Epstein–Barr virus subtypes associated with high risk of nasopharyngeal carcinoma

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. ChangVincent 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

Research output: Contribution to journal › Article › peer-review

121 Scopus citations

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 × 10⁻²⁵ for SNP 162476_C; OR = 6.14, P = 2.40 × 10⁻³² 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.

Original language	English (US)
Pages (from-to)	1131-1136
Number of pages	6
Journal	Nature Genetics
Volume	51
Issue number	7
DOIs	https://doi.org/10.1038/s41588-019-0436-5
State	Published - Jul 1 2019

ASJC Scopus subject areas

Genetics

Access to Document

10.1038/s41588-019-0436-5

Cite this

Xu, M., Yao, Y., Chen, H., Zhang, S., Cao, S. M., Zhang, Z., Luo, B., Liu, Z., Li, Z., Xiang, T., He, G., Feng, Q. S., Chen, L. Z., Guo, X., Jia, W. H., Chen, M. Y., Zhang, X., Xie, S. H., Peng, R., ... Liu, J. (2019). Genome sequencing analysis identifies Epstein–Barr virus subtypes associated with high risk of nasopharyngeal carcinoma. Nature Genetics, 51(7), 1131-1136. https://doi.org/10.1038/s41588-019-0436-5

Xu, M, Yao, Y, Chen, H, Zhang, S, Cao, SM, Zhang, Z, Luo, B, Liu, Z, Li, Z, Xiang, T, He, G, Feng, QS, Chen, LZ, Guo, X, Jia, WH, Chen, MY, Zhang, X, Xie, SH, Peng, R, Chang, ET, Pedergnana, V, Feng, L, Bei, JX, Xu, RH, Zeng, MS, Ye, W, Adami, HO, Lin, X, Zhai, W, Zeng, YX & Liu, J 2019, 'Genome sequencing analysis identifies Epstein–Barr virus subtypes associated with high risk of nasopharyngeal carcinoma', Nature Genetics, vol. 51, no. 7, pp. 1131-1136. https://doi.org/10.1038/s41588-019-0436-5

@article{db5cb823f8dc45a184c802df0b3b29a8,

title = "Genome sequencing analysis identifies Epstein–Barr virus subtypes associated with high risk of nasopharyngeal carcinoma",

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 × 10−25 for SNP 162476_C; OR = 6.14, P = 2.40 × 10−32 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.",

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

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2019",

month = jul,

day = "1",

doi = "10.1038/s41588-019-0436-5",

language = "English (US)",

volume = "51",

pages = "1131--1136",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "7",

}

TY - JOUR

T1 - Genome sequencing analysis identifies Epstein–Barr virus subtypes associated with high risk of nasopharyngeal carcinoma

AU - Xu, Miao

AU - Yao, Youyuan

AU - Chen, Hui

AU - Zhang, Shanshan

AU - Cao, Su Mei

AU - Zhang, Zhe

AU - Luo, Bing

AU - Liu, Zhiwei

AU - Li, Zilin

AU - Xiang, Tong

AU - He, Guiping

AU - Feng, Qi Sheng

AU - Chen, Li Zhen

AU - Guo, Xiang

AU - Jia, Wei Hua

AU - Chen, Ming Yuan

AU - Zhang, Xiao

AU - Xie, Shang Hang

AU - Peng, Roujun

AU - Chang, Ellen T.

AU - Pedergnana, Vincent

AU - Feng, Lin

AU - Bei, Jin Xin

AU - Xu, Rui Hua

AU - Zeng, Mu Sheng

AU - Ye, Weimin

AU - Adami, Hans Olov

AU - Lin, Xihong

AU - Zhai, Weiwei

AU - Zeng, Yi Xin

AU - Liu, Jianjun

PY - 2019/7/1

Y1 - 2019/7/1

N2 - 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 × 10−25 for SNP 162476_C; OR = 6.14, P = 2.40 × 10−32 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.

AB - 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 × 10−25 for SNP 162476_C; OR = 6.14, P = 2.40 × 10−32 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.

UR - http://www.scopus.com/inward/record.url?scp=85067843825&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85067843825&partnerID=8YFLogxK

U2 - 10.1038/s41588-019-0436-5

DO - 10.1038/s41588-019-0436-5

M3 - Article

C2 - 31209392

AN - SCOPUS:85067843825

SN - 1061-4036

VL - 51

SP - 1131

EP - 1136

JO - Nature Genetics

JF - Nature Genetics

IS - 7

ER -

Genome sequencing analysis identifies Epstein–Barr virus subtypes associated with high risk of nasopharyngeal carcinoma

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this