Meta-analysis of 990 EBV genomes identifies EBER2 SNP7048 and its interaction with HLA-A*11:01 driving nasopharyngeal carcinoma risk.
Ching-Yuan Wang, Fei Yao, Xinyi Zhang et al.
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In 30 seconds
This meta-analysis examined whether EBV genetic variation and host genetics are associated with nasopharyngeal carcinoma (NPC) across endemic populations in Singapore, Hong Kong, and China’s Guangdong and Guangxi provinces. It combined whole-genome data from 990 EBV genomes with host genetic analyses and phylogenetic comparisons. EBV strains carrying EBER2 SNP7048 were consistently associated with NPC and were estimated to account for approximately 68% of attributable risk in Southeast Asia. Among people carrying a high-risk strain, absence of the HLA-A*11:01 protective allele was associated with a 30.9-fold increase in NPC risk.
Key findings
- EBV strains carrying EBER2 SNP7048 were associated with NPC across the studied populations and accounted for approximately 68% of attributable risk in Southeast Asia.
- People carrying a high-risk EBV strain without the HLA-A*11:01 protective allele had a 30.9-fold increase in NPC risk.
- Phylogenetic analysis indicated that high-risk EBV lineages spread through Southeast Asia by clonal expansion from Southern China.
Why it matters
The findings link a specific EBV variant with NPC risk across several endemic populations and suggest that host immune genetics modifies that association. This provides a framework for studying how viral lineage and inherited susceptibility jointly shape population risk, while underscoring that infection alone does not capture the reported variation in NPC risk.
What to keep in mind
The analysis covered cohorts from Singapore, Hong Kong, and Guangdong and Guangxi provinces; its findings may not generalise to populations outside these regions.