Introduction:
Recent studies have highlighted the potential roles of immune cells and serum metabolites in the progression of ovarian cancer (OC). Therefore, this study used Mendelian randomization (MR) methodology to investigate potential causal associations among serum metabolites, immune cells, and OC.

Material and methods:
This study used data from multiple sources to obtain genetic data related to immune cell phenotypes, serum metabolites, and OC. Causal effects were estimated using the inverse variance weighted, MR-Egger, weighted median, simple mode, and weighted mode methods to assess potential causal effects. Finally, mediation analysis was conducted to investigate the potential mediating roles of immune cell phenotypes and serum metabolites in OC.

Results:
Thirty-six causal associations between immune cell phenotypes and OC were identified. “Resting CD4 regulatory T cell %CD4 regulatory T cell” (OR = 0.977, p = 0.018) was associated with a lower risk of OC, while “IgD- CD38dim B cell %B cell” (OR = 1.027, p = 0.021) was associated with a higher risk of OC. Additionally, 89 causal associations were identified between serum metabolites and OC. “Gluconate levels” (OR = 0.925, p = 0.047) was associated with a lower risk of OC, while “fructose levels” (OR = 1.097, p = 0.019) was associated with a higher risk of OC. Mediation analysis identified 3 serum metabolites that potentially mediated the influence of immune cell phenotypes on OC, alongside 2 immune cell phenotypes acting as potential mediators between serum metabolites and OC. Notably, sensitivity analysis supported the robustness of these findings.

Conclusions:
This work provides novel insights into the potential causal associations among immune cells, serum metabolites, and OC.