Abstract
While observational studies have identified associations between gastroesophageal reflux disease (GERD) and laryngeal cancer (LC), the causal direction remains undetermined. This study employed a bidirectional 2-sample Mendelian randomization (MR) approach complemented by meta-analysis to investigate potential causal relationships between GERD and LC. Analysis leveraged publicly accessible genome-wide association study resources. Instrumental variables meeting MR assumptions were rigorously selected. The inverse variance weighted method served as primary analysis, with horizontal pleiotropy assessed through MR-Egger intercept tests. Sensitivity evaluations included Cochran Q test for heterogeneity and leave-one-out analysis. Findings from multiple databases were consolidated via meta-analysis. Inverse variance weighted estimates demonstrated no significant causal effect of GERD on LC risk (odds ratio [OR] = 1.11, 95% confidence interval [CI] = 0.83-1.48). In addition, reverse MR analysis revealed no causal impact of LC genetic liability on GERD development (odds ratio = 1.01, 95% CI = 0.99-1.02). All sensitivity analyses supported consistent results. This bidirectional MR investigation provides no genetic evidence for causal associations between GERD and LC in either direction.