Assessing the relationship between gut microbiota and oropharynx cancer:a two-sample Mendelian randomization analysis

Abstract Background Growing evidence suggests that gut microbiota is closely related to the risk of oropharynx cancer (OPC), but whether there is a causal effect remains unknown. In this study, we adopted a Mendelian randomization (MR) approach to evaluate the potential causal relationships between gut microbiota and the risk of OPC. Methods We identified genetic instrumental variables for gut microbiota from a genome-wide association study (GWAS) of 18,340 participants. Summary statistics of oropharynx cancer were drawn from a GWAS Catalog including 9,981 cases and 437,924 controls. Our main analyses were conducted using the inverse-variance weighted (IVW) method with random-effects model, complemented by the other two analyses: weighted median method and MR-Egger approach. We also performed reverse MR analysis to evaluate the possibility of reverse causation. Results We identified suggestive associations between four bacterial traits and the risk of OPC: the odds ratio (OR) was 2.74 (95% confidence interval [CI]: 1.57, 4.78; p = 0.00041) for genus Hungatella; OR was 0.53 (95% CI: 0.33, 0.85; p = 0.0087) for family Rikenellaceae; OR was 0.44 (95% CI: 0.23, 0.84; p = 0.012) for genus Alistipes, and OR was 0.56 (95% CI: 0.38, 0.82; p = 0.0029) for phylum Lentisphaerae. The results of sensitivity analyses for these bacterial traits were consistent. We did not find statistically significant associations between OPC and these four bacterial traits in the reverse MR analysis. Conclusions Our systematic analyses provide evidence to support a potential causal relationship between several gut microbiota taxa and the risk of oropharynx cancer. Further studies are required to investigate how the gut microbiota affects the development of OPC.