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

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

Nature genetics, 2019-07, Vol.51 (7), p.1131-1136 [Periódico revisado por pares]

United States: Nature Publishing Group

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Genome sequencing analysis identifies Epstein-Barr virus subtypes associated with high risk of nasopharyngeal carcinoma
Autor: Xu, Miao ; Yao, Youyuan ; Chen, Hui ; Zhang, Shanshan ; Cao, Su-Mei ; Zhang, Zhe ; Luo, Bing ; Liu, Zhiwei ; Li, Zilin ; Xiang, Tong ; He, Guiping ; Feng, Qi-Sheng ; Chen, Li-Zhen ; Guo, Xiang ; Jia, Wei-Hua ; Chen, Ming-Yuan ; Zhang, Xiao ; Xie, Shang-Hang ; Peng, Roujun ; Chang, Ellen T ; Pedergnana, Vincent ; Feng, Lin ; Bei, Jin-Xin ; Xu, Rui-Hua ; Zeng, Mu-Sheng ; Ye, Weimin ; Adami, Hans-Olov ; Lin, Xihong ; Zhai, Weiwei ; Zeng, Yi-Xin ; Liu, Jianjun
Assuntos: Bioinformatics ; Cancer ; Case-Control Studies ; China ; China - epidemiology ; DNA sequencing ; DNA-Binding Proteins ; DNA-Binding Proteins - genetics ; Epidemics ; Epstein-Barr virus ; Epstein-Barr Virus Infections ; Epstein-Barr Virus Infections - complications ; Epstein-Barr Virus Infections - virology ; Gene sequencing ; Genetic aspects ; Genome, Viral ; Genomes ; Haplotypes ; Herpesvirus 4, Human ; Herpesvirus 4, Human - classification ; Herpesvirus 4, Human - genetics ; Herpesvirus 4, Human - isolation & purification ; Human health and pathology ; Humans ; Infections ; Life Sciences ; Lymphoma ; Medicin och hälsovetenskap ; Nasopharyngeal cancer ; Nasopharyngeal Carcinoma ; Nasopharyngeal Carcinoma - epidemiology ; Nasopharyngeal Carcinoma - genetics ; Nasopharyngeal Carcinoma - virology ; Nasopharyngeal Neoplasms ; Nasopharyngeal Neoplasms - epidemiology ; Nasopharyngeal Neoplasms - genetics ; Nasopharyngeal Neoplasms - virology ; Nucleotide sequencing ; Phylogenetics ; Phylogeny ; Polymorphism, Single Nucleotide ; Principal components analysis ; Risk analysis ; Risk factors ; Studies ; Throat cancer ; Viral Proteins ; Viral Proteins - genetics ; Viruses
É parte de: Nature genetics, 2019-07, Vol.51 (7), p.1131-1136
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SourceType-Scholarly Journals-1
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PMCID: PMC6610787
Y.-X.Z., J.L., and W.Z. were the principal investigators who conceived the study. Y.-X.Z., J.L., W.Z., and M.X. designed and oversaw the study. J.L. and X.L. supervised the viral genome-wide association studies. W.W. supervised phylogenetic analysis. M.X. contributed sample preparation, sequencing, genotyping, variant calling and genetic statistical analyses. Y.Y. contributed sequencing, genotyping and variant calling. H.C. contributed phylogenetic analyses. S.Z. contributed to genotyping and genetic statistical analyses. Z.Li contributed genetic statistical analyses. Z.Z. contributed collecting samples from the First Affiliated Hospital of Guangxi Medical College. B.L. contributed collecting samples from the Affiliated Hospital of the Qingdao University. X.G. contributed collecting samples from Sun Yat-sen University Cancer Center (SYSUCC). M.-Y.C. contributed collecting samples from SYSUCC. R.P. contributed collecting samples from SYSUCC. R.-H. X. contributed collecting samples from SYSUCC. H.-O.A., W.Y., and Y.-X.Z. supervised the design and implementation of the population-based case-control study in Zhaoqing. W.Y., E.T.C., S.-M.C., S.-H.X., and Z.Liu participated in the case-control study. The manuscript was drafted by M.X., J.L., W.Z., and Y.-X.Z. and revised by V.P. and E.T.C.. All the authors critically reviewed the article and approved the final manuscript.
Author contributions
Descrição: 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 for SNP 162476_C; OR = 6.14, P = 2.40 × 10 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.
Editor: United States: Nature Publishing Group
Idioma: Inglês

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

United States: Nature Publishing Group

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