Abstract
BACKGROUND: Previous studies indicated that atrial fibrillation (AF) patients had a significantly higher esophageal cancer (EC) risk. However, influencing by confounding factors, the causal effect is uncertain. In this study, we aimed to validate the causal relationship between AF and EC by Mendelian randomization (MR) analysis. METHODS: An observational analysis was conducted using the data from the National Health and Nutrition Examination Survey (NHANES) and UK Biobank. Then a two-sample MR method was employed to assess the causal effect of AF on EC. The exposure of AF was collected from publicly available genome-wide association studies (GWASs). Meanwhile, the EC outcome data were derived from the UK Biobank and the FinnGen consortium. A set of 108 single-nucleotide polymorphisms (SNPs) served as instrumental variables (IVs). The effect estimates were calculated using the inverse variance weighted (IVW) method. RESULTS: Genetically predicted AF was associated with an increased risk of EC [odds ratio (OR), 1.73; 95% confidence interval (CI): 1.01-1.73; P=0.04]. The similar results could be found by sensitivity analyses and no any evidence of horizontal pleiotropy was observed. CONCLUSIONS: This two-sample MR analysis suggested that AF was causally associated with an increased risk of EC.