Unveiling familial aggregation of nasopharyngeal carcinoma: Insights from oral microbiome dysbiosis.

Familial aggregation is common in nasopharyngeal carcinoma (NPC), yet the impact of oral microbiome dysbiosis on this occurrence remains largely unexplored. We recruit 127 families (649 members, 1-5 patients each) and a case-control cohort of 337 individuals, validating findings in an additional cohort of 995 individuals. Significant microbial similarity is observed among family members, with family factors contributing most to microbiome variation, followed by cigarette smoking, age, and gender. Among multi-NPC families, especially those with three or more patients, we identify three NPC-enriched taxa with notable heritability, including Gemella sp. (heritability, h = 53.1%), Lautropia mirabilis (h = 38.8%), and Streptococcus sp. (h = 38.0%). Heritable bacteria present a markedly higher heritability in families with increased clustering of NPC and form closely interacting networks, suggesting their role in NPC familial aggregation. These findings open up possibilities for identifying high-risk individuals, enhancing clinical surveillance, and developing personalized prevention and treatment approaches of NPC through microbiome-based strategies.