Causal relationship between gut microbiota and vulvar cancer: a two-sample bi-directional Mendelian randomization study

Objective: Recent investigations have proposed a link between gut microbiomes (GMs) and various cancers, yet the involvement of GMs in vulvar cancer (VC) remains unclear. The objective of this study was to discover the causal association between GMs and VC and identify the GM taxa with potential effect. Methods: Utilizing Mendelian randomization (MR) with genome-wide association study (GWAS) summary statistics, we analyzed 211 GM taxa and 190 VC cases with 167,189 healthy controls. The main analysis used the inverse-variance weighted (IVW) approach, complemented by weighted median test, MR-PRESSO global test, and leave-one-out analysis. Results: Four nominally significant causal relationships were identified between GM taxa and VC. Class Betaproteobacteria [odds ratio (OR)=0.064, 95% confidence interval (CI): 0.004-0.946, fp=0.045], order Burkholderiales [OR=0.074, 95% CI: 0.009-0.630, p=0.017], genus Intestinibacter [OR=0.073, 95% CI: 0.009-0.617, p=0.016], and genus RuminococcaceaeUCG003 [OR=0.162, 95% CI: 0.028-0.938, p=0.042] were linked to a lower chance of VC. The MR-Egger intercept test and MR-PRESSO global test confirmed the lack of horizontal pleiotropy (p>0.05), and leave-one-out analysis indicated result robustness. Conclusion: Our findings highlight four potential causal relationships and specific intestinal flora associated with decreased VC risk, offering insights for VC prevention and treatment.