A causal association between Epstein-Barr virus infection and lung cancer: A two-sample Mendelian Randomization study.

BackgroundThe association between Epstein-Barr virus (EBV) and lung cancer risk remains controversial. Here, we used a two-sample Mendelian randomization (MR) analysis to test the causal relationship between EBV and lung cancer.MethodsData regarding lung cancer (outcomes) were collected from the Finnish database; the Genome-Wide Association Study (GWAS) summary-level dataset for EBV was obtained from the Open Forum Infect Dis. The inverse-variance weighted (IVW) method was used as a primary analytical approach; weighted median, MR-Egger, and weighted mode methods were used to ensure the robustness of the data. The MR-Egger regression assessed horizontal pleiotropy, and the MR pleiotropy residual sum and outlier (MR-PRESSO) method identified potential outliers. Cochran's Q test evaluated heterogeneity among instrumental variables (IVs).ResultsIVW analysis indicated several significant causal effects. Genetically elevated levels of EBV ZEBRA and EBNA-1 antibodies increased the risk of SQC (OR=1.26 and OR=1.33, respectively). Increased EBNA-1 antibodies also raised the risk of overall lung cancer and small cell lung cancer. Conversely, higher VCA p18 antibody levels were associated with a decreased risk of lung adenocarcinoma (OR=0.70). Sensitivity analyses suggested these findings were robust, with no significant evidence of horizontal pleiotropy or heterogeneity.ConclusionOur data suggests a causal effect between EBV and the progression of lung cancer.