The triad of nasopharyngeal carcinoma pathogenesis: host genetics, viral infection, and environmental exposures

Nasopharyngeal carcinoma (NPC) are geographically restricted malignancies, exhibiting significantly higher incidence in specific regions and among certain ethnic groups, indicating strong genetic and region-specific etiological influences. The pathogenesis of these malignancies illustrates a multifaceted interaction involving host genetic predisposition, viral infections, as well as various environmental and lifestyle factors. This mini review brings together existing evidence regarding the molecular genetic factors influencing both EBV and HR-HPV-associated NPC, focusing on gene polymorphisms, viral biomarkers, and risk modifiers that vary across populations. Recurrent genetic associations involved polymorphisms in GSTM1, CYP1A1, XRCC1, TNF, HLA microsatellites, and xenobiotic metabolism genes, particularly CYP2A6. Markers linked to EBV, including LMP1, EBNA1, and circulating plasma EBV DNA, exhibited a consistent association with NPC susceptibility. Similarly, HR-HPV markers including E6 and E7 oncoproteins, p16INK4a overexpression, and HPV DNA detection serve as critical biomarkers for HPV-driven HNCs, but categorically these associations haven’t yet been discovered in regard to NPC. These findings classify NPC as a genetically modified, virus-related cancer and highlight the necessity for population-specific genetic risk assessment, EBV / HPV-derived biomarkers, and targeted preventative efforts.