Genome sequencing analysis identifies Epstein–Barr virus subtypes associated with high risk of nasopharyngeal carcinoma
Miao Xu
(1, 2)
,
Youyuan Yao
(1)
,
Hui Chen
(3)
,
Shanshan Zhang
(1)
,
Su-Mei Cao
(1)
,
Zhe Zhang
,
Bing Luo
(4)
,
Zhiwei Liu
(5)
,
Zilin Li
(2)
,
Tong Xiang
(1)
,
Guiping He
(1)
,
Qi-Sheng Feng
(1)
,
Li-Zhen Chen
(1)
,
Xiang Guo
(1)
,
Wei-Hua Jia
(1)
,
Ming-Yuan Chen
(1)
,
Xiao Zhang
(1)
,
Shang-Hang Xie
(1)
,
Roujun Peng
(1)
,
Ellen Chang
(6)
,
Vincent Pedergnana
(3, 7)
,
Lin Feng
(1)
,
Jin-Xin Bei
(1)
,
Rui-Hua Xu
(1)
,
Mu-Sheng Zeng
(1)
,
Weimin Ye
(5)
,
Hans-Olov Adami
(2, 5)
,
Xihong Lin
(2)
,
Weiwei Zhai
(3, 8)
,
Yi-Xin Zeng
(1)
,
Jianjun Liu
(3, 9)
1
SYSUCC -
Sun Yat-sen University Cancer Center
2 Harvard T.H. Chan School of Public Health
3 GIS - Genome Institute of Singapore
4 QDU - Qingdao University
5 Karolinska Institutet [Stockholm]
6 Stanford Cancer Institute
7 MIVEGEC - Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle
8 Institute of Zoology [Beijing]
9 NUS - National University of Singapore
2 Harvard T.H. Chan School of Public Health
3 GIS - Genome Institute of Singapore
4 QDU - Qingdao University
5 Karolinska Institutet [Stockholm]
6 Stanford Cancer Institute
7 MIVEGEC - Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle
8 Institute of Zoology [Beijing]
9 NUS - National University of Singapore
Hui Chen
- Fonction : Auteur
- PersonId : 768630
- ORCID : 0000-0002-0440-8156
Shanshan Zhang
- Fonction : Auteur
- PersonId : 798805
- ORCID : 0000-0002-9033-3786
Zhe Zhang
- Fonction : Auteur
Zhiwei Liu
- Fonction : Auteur
- PersonId : 782488
- ORCID : 0000-0002-0136-651X
Ming-Yuan Chen
- Fonction : Auteur
- PersonId : 828279
- ORCID : 0000-0003-4793-0902
Vincent Pedergnana
- Fonction : Auteur
- PersonId : 174866
- IdHAL : vincent-pedergnana
- ORCID : 0000-0002-7852-5339
- IdRef : 175475547
Lin Feng
- Fonction : Auteur
- PersonId : 828280
- ORCID : 0000-0001-6461-5838
Jin-Xin Bei
- Fonction : Auteur
- PersonId : 794757
- ORCID : 0000-0003-1333-407X
Rui-Hua Xu
- Fonction : Auteur
- PersonId : 803953
- ORCID : 0000-0001-9771-8534
Mu-Sheng Zeng
- Fonction : Auteur
- PersonId : 828281
- ORCID : 0000-0003-3509-5591
Weiwei Zhai
- Fonction : Auteur
- PersonId : 771170
- ORCID : 0000-0001-7938-0226
Yi-Xin Zeng
- Fonction : Auteur
- PersonId : 794758
- ORCID : 0000-0002-6515-628X
Jianjun Liu
- Fonction : Auteur
- PersonId : 764292
- ORCID : 0000-0002-3255-3019
Résumé
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.