Oral Microbiota and Pharyngeal-Laryngeal Cancer Risk: Evidence from Mendelian Randomization in East Asian Populations

Pharyngeal and laryngeal cancer (PLC) encompasses a range of aggressive malignancies associated with substantial clinical impact, underscoring the need for novel preventive and therapeutic measures. Mendelian randomization (MR) serves as an effective methodology for assessing causal associations based on genetic variants as instrumental tools. It reduces biases such as confounding and reverse causation prevalent in traditional observational studies. This research sought to investigate the causal relationships between oral microbial taxa and PLC using a two-sample MR approach. The goal was to identify specific oral microbiota that may directly contribute to the development of PLC and could serve as potential biomarkers or targets for therapeutic intervention. A two-sample MR analysis was conducted to assess the causal impact of 3,117 oral microbial taxa on the risk of PLC. Instrumental variables (IVs) were selected based on genome-wide significance (p < 1 × 10^-5), minimal linkage disequilibrium (r² < 0.001), and robust strength (F > 10). The primary evaluation employed the inverse-variance weighted (IVW) approach, complemented by sensitivity analyses (including weighted median, weighted mode, simple mode, MR-Egger regression, and MR-PRESSO) to account for pleiotropy and heterogeneity. Bidirectional MR was performed to examine possible reverse causation. The forward MR analysis identified 14 oral microbial taxa that are casually linked to PLC risk (p < 0.01). Seven taxa were associated with elevated PLC risk, with odds ratios spanning 2.51 to 3.23, whereas seven taxa demonstrated protective effects, with odds ratios ranging from 0.36 to 0.52. Sensitivity analyses, encompassing Cochran's Q test, MR-Egger intercept, and MR-PRESSO, validated the reliability of these results, indicating no notable heterogeneity or pleiotropy. Bidirectional MR analyses detected no evidence of reverse causation, suggesting that these oral microbiotas likely act as upstream contributors to PLC development rather than downstream outcomes. This MR analysis identifies 14 oral microbial taxa causally linked to PLC, with seven increasing risk and seven conferring protections. These findings underscore the role of oral microbiota in PLC pathogenesis and highlight potential microbial mechanisms. Further research is needed to elucidate their roles and explore their use as biomarkers or therapeutic targets.