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BMC Oral Health
Published in: BMC Oral Health 1/2024

Open Access 01-12-2024 | Cytokines | Research

Inflammatory cytokines mediating the effect of oral lichen planus on oral cavity cancer risk: a univariable and multivariable mendelian randomization study

Authors: Tao Zheng, Chengyong Liu, Yetong Wang, Han Zhou, Rong Zhou, Xuan Zhu, Zibing Zhu, Yisi Tan, Zhengrui Li, Xufeng Huang, Jin Tan, Keke Zhu

Published in: BMC Oral Health | Issue 1/2024

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Abstract

Background

While observational studies and experimental data suggest a link between oral lichen planus (OLP) and oral cavity cancer (OCC), the causal relationship and the role of inflammatory cytokines remain unclear.

Methods

This study employed a univariable and multivariable Mendelian Randomization (MR) analysis to investigate the causal relationship between OLP and the risk of OCC. Additionally, the potential role of inflammatory cytokines in modulating this association was explored. Instrumental variables were derived from genetic variants associated with OLP (n = 377,277) identified in Finngen R9 datasets, with 41 inflammatory cytokines as potential mediators, and OCC (n = 4,151) as the outcome variable. Analytical methods including Inverse Variance Weighted (IVW), Weighted Median, MR-Egger, and MR-PRESSO were utilized to assess the causal links among OLP, inflammatory cytokines, and OCC risk. Multivariable MR (MVMR) was then applied to quantify the mediating effects of these cytokines in the relationship between OLP and increased OCC risk.

Results

MR analysis provided strong evidence of a causal relationship between OLP (OR = 1.417, 95% CI = 1.167–1.721, p < 0.001) and the risk of OCC. Furthermore, two inflammatory cytokines significantly influenced by OLP, IL-13 (OR = 1.088, 95% CI: 1.007–1.175, P = 0.032) and IL-9 (OR = 1.085, 95% CI: 1.005–1.171, P = 0.037), were identified. Subsequent analysis revealed a significant causal association only between IL-13 (OR = 1.408, 95% CI: 1.147–1.727, P = 0.001) and higher OCC risk, establishing it as a potential mediator. Further, MVMR analysis indicated that IL-13 (OR = 1.437, 95% CI = 1.139–1.815, P = 0.002) mediated the relationship between OLP and OCC, accounting for 8.13% of the mediation.

Conclusion

This study not only elucidates the potential causal relationship between OLP and the risk of OCC but also highlights the pivotal mediating role of IL-13 in this association.
Appendix
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Metadata
Title
Inflammatory cytokines mediating the effect of oral lichen planus on oral cavity cancer risk: a univariable and multivariable mendelian randomization study
Authors
Tao Zheng
Chengyong Liu
Yetong Wang
Han Zhou
Rong Zhou
Xuan Zhu
Zibing Zhu
Yisi Tan
Zhengrui Li
Xufeng Huang
Jin Tan
Keke Zhu
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Oral Health / Issue 1/2024
Electronic ISSN: 1472-6831
DOI
https://doi.org/10.1186/s12903-024-04104-0

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