Genomic landscape of Epstein–Barr virus in familial nasopharyngeal carcinoma. (29th March 2022)

• Record Type: Journal Article
• Authors: Zhang, Wen-Li; Zhang, Jiang-Bo; Wang, Tong-Min; Wu, Yan-Xia; He, Yong-Qiao; Xue, Wen-Qiong; Liao, Ying; Deng, Chang-Mi; Li, Dan-Hua; Wu, Zi-Yi; Yang, Da-Wei; Zheng, Xiao-Hui; Li, Xi-Zhao; Zhou, Ting; Zhang, Pei-Fen; Zhang, Shao-Dan; Hu, Ye-Zhu; Jia, Wei-Hua
• Is Part Of: Journal of general virology. Volume 103:Number 3(2022)
• Publication Date: 2022-03-29
• Subjects: Epstein–Barr virus -- nasopharyngeal carcinoma -- familial aggregation -- genetic variation; Virology -- Periodicals; Viruses; Microbiology; Virology; Virologie -- Périodiques; Microbiologie -- Périodiques; Virology; Virologie; Virologie; Electronic journals; Periodical; Periodicals; 579.2
• DOI: 10.1099/jgv.0.001728
• Languages: English
• ISSNs: 0022-1317

Abstract

Abstract : To better understand the genomic characteristics of Epstein–Barr virus (EBV) in familial nasopharyngeal carcinoma (NPC), we sequenced the EBV genomes by whole-genome capture in 38 unrelated patients with NPC family history in first-degree relatives and 47 healthy controls, including 13 with family history and 34 without. Compared with type 1 reference genome, mutation hotspots were observed in the latent gene regions of EBV in familial NPC cases. Population structure analysis showed that one cluster has a higher frequency in familial cases than in controls (OR=5.33, 95 % CI 2.50–11.33, P =1.42×10 −5 ), and similar population structure composition was observed among familial and sporadic NPC cases in high-endemic areas. By genome-wide association analysis, four variants were found to be significantly associated with familial NPC. Consistent results were observed in the meta-analysis integrating two published case-control EBV sequencing studies in NPC high-endemic areas. High-risk haplotypes of EBV composed of 34 variants were associated with familial NPC risk (OR=13.85, 95 % CI 4.13–46.44, P =2.06×10 −5 ), and higher frequency was observed in healthy blood-relative controls with NPC family history (9/13, 69.23 %) than those without family history (16/34, 47.06%). This study suggested the potential contribution of EBV high-risk subtypes to familial aggregation of NPC.