1887

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, =1.42×10), 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, =2.06×10), 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.

Funding
This study was supported by the:
  • Key Area Research and Development Program of Guangdong Province (Award 2019B110233004)
    • Principle Award Recipient: Xiao-HuiZheng
  • the Sino-Sweden Joint Research Program (Award 81861138006)
    • Principle Award Recipient: Wei-HuaJia
  • Science and Technology Planning Project of Guangdong Province (Award 2019B030316031)
    • Principle Award Recipient: Wei-HuaJia
  • the Science and Technology Planning Project of Guangzhou (Award 201904010467)
    • Principle Award Recipient: Xiao-HuiZheng
  • National Natural Science Foundation of China (Award 82003520)
    • Principle Award Recipient: Tong-MinWang
  • National Natural Science Foundation of China (Award 81903395)
    • Principle Award Recipient: Yong-QiaoHe
  • National Natural Science Foundation of China (Award 81802708)
    • Principle Award Recipient: Xiao-HuiZheng
  • National Natural Science Foundation of China (Award 81973131)
    • Principle Award Recipient: Wei-HuaJia
  • the Special Support Program for High-level Professionals on Scientific and Technological Innovation of Guangdong Province (Award 2014TX01R201)
    • Principle Award Recipient: Wei-HuaJia
  • Basic and Applied Basic Research Foundation of Guangdong Province (Award 2021B1515420007)
    • Principle Award Recipient: Wei-HuaJia
  • Natural Science Foundation of Guangdong Province (Award 2021A1515012397)
    • Principle Award Recipient: Jiang-BoZhang
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/content/journal/jgv/10.1099/jgv.0.001728
2022-03-29
2024-07-24
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