Exploration of the Causal Associations Between Circulating Inflammatory Factors, Metabolites, And Cervical Cancer: A Bidirectional Mendelian Randomization Study And Mediation Analysis

Cong Xu; Guangming Wang; Yonghong Xu

doi:10.62051/ijphmr.v4n3.01

Authors

Cong Xu
Guangming Wang
Yonghong Xu

DOI:

https://doi.org/10.62051/ijphmr.v4n3.01

Keywords:

Inflammatory factors, Cervical cancer, Mendelian randomization, Mediation analyses, Metabolite

Abstract

Although numerous studies have demonstrated the critical role that inflammatory factors play in the onset and progression of different malignancies, their causal relationship with cervical cancer and the putative metabolite mediators is still unknown. Our study design incorporates the direct correlation and mediating role of metabolites in the relationship between inflammatory factors and cervical cancer. The data for this article comes from multiple queues and consortia, including the FinnGen database. We conducted comprehensive pairwise genetic analysis and used a mediated Mendelian randomization (MR) design to assess the causal effect of inflammatory factors on cervical cancer. The causality in mediation analysis is optimized in this work. To investigate the causative relationship between inflammatory factors and cervical cancer, as well as the mediating function of metabolites through inverse variance weighted (IVW), mainly a two-step, bidirectional Mendelian randomization research was utilized. As supplementary analysis techniques, other techniques, including MR-Egger, Weighted median (WM), Simple mod, and Weighted mode were also used. One inflammatory factor (C-C motif chemokine 28) was found to have a protective effect on CC by MR analysis. These inflammatory factors may also have an impact on CC via changing the metabolite (Alpha−hydroxyisovalerate). When it comes to cervical cancer, the mediated impact of alpha-hydroxyisovalerate is 0.0417(-0.0989, 0.182) and the causal effect of C-C motif chemokine 28 is the total effect IVW: OR = 0.606, 95% CI [0.397–0.926], p = 0.020. -8.34% is the mediated fraction (19.8%, -36.4%). This finding points to an alpha-hydroxyisovalerate-mediated causal link between C-C motif chemokine 28 and cervical cancer. Our results demonstrate the intricate connection between metabolites, inflammatory factors, and cervical cancer. The associations and mediating effects that have been identified provide valuable insights into potential therapeutic pathways targeting inflammatory factors for the management of cervical cancer.

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