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.

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. GWAS data for GM taxa were sourced from the MiBioGen consortium, and VC data were acquired from the FinnGen consortium. The main analysis used the inverse-variance weighted (IVW) approach, complemented by weighted median, MR-Egger, weighted mode, and simple mode approaches. Sensitivity analyses included Cochrane’s Q-test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis.

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, p=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.

Our findings highlight four potential causal relationships and specific intestinal flora associated with decreased VC risk, offering insights for VC prevention and treatment. Competing Interest Statement The authors have declared no competing interest. Funding Statement This work was jointly supported by National High Level Hospital Clinical Research Funding (Scientific Research Seed Fund of Peking University First Hospital 2023SF08) and Beijing Natural Science Foundation (7244422). Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This investigation examined publicly available datasets. The following links can be used to access this data: https://r9.finngen.fi, https://mibiogen.gcc.rug.nl. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present work are contained in the manuscript