{
  "abstract": "Nasopharyngeal carcinoma (NPC) is a major health burden in East and Southeast Asia (SEA). While EBV infection is a primary driver, the specific viral strains responsible for NPC development and their interaction with host genetics across geographically diverse endemic regions remain poorly understood. We performed a whole-genome sequencing of 388 EBV isolates and matched host whole-exome sequencing in a Singaporean cohort. To define the global significance of these findings, we conducted a meta-GWAS and phylogenetic analysis across three independent cohorts (Singapore, Hong Kong, and Guangdong and Guangxi provinces of China), totaling 990 EBV genomes. Our study identifies high-risk EBV strains—carrying a core variant in the EBER2 locus (SNP7048)—as the key viral determinator of NPC risk, accounting for approximately 68% of the attributable risk in SEA. Meta-analysis reveals these strains are consistently associated with NPC across all populations, resolving previous regional genetic discordances. We demonstrate a potent synergistic interaction between these EBV risk strains and the host HLA-A*11:01 protective allele; individuals lacking this protection while carrying a high-risk strain exhibit a 30.9-fold increase in NPC risk. Phylogenetic analysis further reveals that these high-risk lineages populated SEA through clonal expansion from Southern China, following historical migration routes. These findings establish that NPC development is driven by the distribution of specific high-risk EBV lineages and their synergistic interaction with host immune susceptibility. This provides a definitive genetic framework for precision population screening and early diagnosis of NPC in the endemic regions.",
  "abstract_shown": true,
  "affiliations": [
    "Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Genome, Singapore 138672, Republic of Singapore",
    "Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore 119228, Singapore",
    "Division of Medical Sciences, National Cancer Centre Singapore, Singapore 168583, Singapore",
    "Department of Otolaryngology—Head and Neck Surgery, National University of Singapore, Singapore 119074, Singapore",
    "State Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China",
    "State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, China",
    "Division of Surgical Oncology, National University Cancer Institute, Singapore 119074, Singapore",
    "Division of Medical Oncology, National Cancer Centre Singapore, Singapore 168583, Singapore",
    "Oncology Academic Programme, Duke-NUS Medical School, Singapore 169857, Singapore",
    "Division of Radiation Oncology, National Cancer Centre Singapore, Singapore 168583, Singapore",
    "Centre for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 23,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Ching-Yuan Wang",
      "orcid": "0009-0007-3624-7880"
    },
    {
      "affs": [
        0
      ],
      "name": "Fei Yao"
    },
    {
      "affs": [
        0
      ],
      "name": "Xinyi Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Ling Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yee Yen Sia"
    },
    {
      "affs": [
        2
      ],
      "name": "Enya Hui Wen Ong"
    },
    {
      "affs": [
        2
      ],
      "name": "Eugenia Li Ling Yeo"
    },
    {
      "affs": [
        0
      ],
      "name": "Andrea Nicole Rio"
    },
    {
      "affs": [
        3
      ],
      "name": "Chor Hiang Siow"
    },
    {
      "affs": [
        3
      ],
      "name": "Han Lee Goh"
    },
    {
      "affs": [
        3
      ],
      "name": "Zhi Kang Chin"
    },
    {
      "affs": [
        3
      ],
      "name": "Rachel Jia Xuan Ng"
    },
    {
      "affs": [
        3
      ],
      "name": "Ying Yu Tan"
    },
    {
      "affs": [
        3
      ],
      "name": "Javier Cher An Chee",
      "orcid": "0009-0006-8929-5053"
    },
    {
      "affs": [
        3
      ],
      "name": "Wei Keat Teo"
    },
    {
      "affs": [
        4
      ],
      "name": "Weiwei Zhai",
      "orcid": "0000-0001-7938-0226"
    },
    {
      "affs": [
        5
      ],
      "name": "Yanhong Chen"
    },
    {
      "affs": [
        5
      ],
      "name": "Miao Xu",
      "orcid": "0000-0001-7091-4199"
    },
    {
      "affs": [
        3,
        6
      ],
      "name": "Kwok Seng Loh"
    },
    {
      "affs": [
        2,
        7,
        8
      ],
      "name": "Wan-Teck Lim",
      "orcid": "0000-0002-4655-0206"
    },
    {
      "affs": [
        2,
        8,
        9
      ],
      "name": "Melvin Lee Kiang Chua"
    },
    {
      "affs": [
        3,
        6,
        10
      ],
      "name": "Joshua K. Tay",
      "orcid": "0000-0001-5653-4659"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jianjun Liu",
      "orcid": "0000-0002-3255-3019"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5bhmhzmed0bs1.bib",
  "cited_by": 0,
  "doi": "10.1073/pnas.2617057123",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13715771/",
  "id": "5bhmhzmed0bs1",
  "issns": [
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  "landing_url": "https://doi.org/10.1073/pnas.2617057123",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
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  "native_subjects": [
    [
      "heading",
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    [
      "heading",
      "Biological Sciences"
    ],
    [
      "heading",
      "Population Biology"
    ],
    [
      "openalex",
      "2730|Viral-associated cancers and disorders"
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  "pdf_url": null,
  "pmcid": "PMC13715771",
  "pmid": "42900724",
  "published": "2026-10-20",
  "publisher": "National Academy of Sciences",
  "ris": "https://research.draconitic.com/paper/5bhmhzmed0bs1.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T12:22:58Z",
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      "field": "medicine",
      "origin": "openalex:2730|Viral-associated cancers and disorders",
      "subfield": "oncology"
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  ],
  "title": "Meta-analysis of 990 EBV genomes identifies EBER2 SNP7048 and its interaction with HLA-A*11:01 driving nasopharyngeal carcinoma risk",
  "title_text": "Meta-analysis of 990 EBV genomes identifies EBER2 SNP7048 and its interaction with HLA-A*11:01 driving nasopharyngeal carcinoma risk",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:22:58Z",
  "url": "https://research.draconitic.com/paper/5bhmhzmed0bs1",
  "venue": "Proceedings of the National Academy of Sciences of the United States of America",
  "versions": []
}