Exploring the causal relationship between obesity, immune cell characteristics and cervical cancer risk using Mendelian randomization

Abstract Background Cervical cancer is a common malignancy among women worldwide. Obesity has been linked to numerous cancers through mechanisms involving hormonal disruption and chronic inflammation, while immune function variations may influence individual cancer susceptibility. However, the causa...

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Bibliographic Details
Main Authors: HongYin Cui, Jingjing Zhang, Xiaolin Lang, Changchang Huang, SongQing Yang
Format: Article
Language:English
Published: Springer 2025-07-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-03111-z
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Summary:Abstract Background Cervical cancer is a common malignancy among women worldwide. Obesity has been linked to numerous cancers through mechanisms involving hormonal disruption and chronic inflammation, while immune function variations may influence individual cancer susceptibility. However, the causal relationships between obesity, immune characteristics, and cervical cancer development remain unclear. Methods This study employed Mendelian randomization (MR) using single nucleotide polymorphisms (SNPs) as genetic instrumental variables to analyze causal relationships between obesity, immune cell composition, HLA expression, and cervical cancer risk. Multiple MR analytical methods (MR Egger, inverse variance weighted, weighted median, and weighted mode) were used for validation, with forest plots, scatter plots, and funnel plots used to assess result robustness. Results Findings regarding obesity and cervical cancer were inconsistent: one analysis showed no significant causal relationship (OR ≈ 1.00, p > 0.05), while another supported a causal association. Specific immune cell populations were positively associated with cervical cancer risk, and HLA expression (particularly HLA-DRB and CD33+/HLA-DR + cells) was linked to increased cervical cancer risk. Notably, CD4+/CD8 + regulatory T cells were negatively associated with cervical cancer risk, suggesting a potential protective effect. Conclusion This study provides genetic epidemiological evidence for potential causal relationships between obesity, immune cell composition, HLA expression, and cervical cancer risk. These findings reveal the importance of immune function in HPV-related carcinogenesis and offer new perspectives for cervical cancer prevention and targeted treatment.
ISSN:2730-6011