Mendelian randomization analysis of risk factors for nasopharyngeal carcinoma: Examining causal links to EBV susceptibility and dietary influences

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a rare but aggressive malignancy that originates in the epithelial cells of the nasopharynx. OBJECTIVES: This study aimed to investigate the causal relationship between Epstein-Barr virus (EBV) susceptibility, dietary factors (specifically preserved food intake), and NPC risk using Mendelian randomization (MR). The goal of this study was to provide insights into the genetic and environmental factors that contribute to NPC pathogenesis. MATERIAL AND METHODS: We performed MR analyses using genome-wide association study (GWAS) data to identify genetic variants associated with EBV susceptibility and preserved food consumption. These genetic variants were used as instrumental variables to assess their causal effects on NPC risk, while controlling for potential confounding and reverse causality. Subgroup and sensitivity analyses, including the MR-Egger, weighted median, and leave-one-out methods, were conducted to evaluate the robustness of the findings. RESULTS: Our MR analysis identified a significant causal effect of EBV genetic susceptibility on NPC risk (β = 1.47, 95% confidence interval (95% CI): 1.12-1.83, p = 0.001). Additionally, genetic predispositions related to higher preserved food intake were associated with an increased risk of NPC (β = 0.75, 95% CI: 0.45-1.05, p = 0.001). Subgroup analysis showed consistent results across different age groups (p for interaction = 0.45), and sensitivity analyses confirmed the robustness of the findings, with no evidence of pleiotropy. CONCLUSIONS: This study provides strong evidence that genetic susceptibility to EBV and preserved food intake are causal risk factors for NPC. These findings offer valuable insights into NPC prevention strategies, particularly in high-risk populations, and highlight the need for further research on gene-environment interactions in NPC pathogenesis.