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. 2024 Mar 22;24(1):375.
doi: 10.1186/s12903-024-04104-0.

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

Tao Zheng  1   2 , Chengyong Liu  2 , Yetong Wang  2 , Han Zhou  2 , Rong Zhou  3 , Xuan Zhu  2 , Zibing Zhu  1 , Yisi Tan  1 , Zhengrui Li  4 , Xufeng Huang  5 , Jin Tan  1 , Keke Zhu  6
Affiliations

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

Tao Zheng et al. BMC Oral Health. .

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 VSports手机版. .

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 V体育安卓版. 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 V体育ios版. 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 VSports最新版本. .

Keywords: Causal inference; Inflammatory cytokines; Mendelian randomisation; Oral cavity cancer; Oral lichen planus V体育平台登录. .

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Conflict of interest statement

The authors declare no competing interests.

"VSports在线直播" Figures

Figure 1
Figure 1
Overview of MR and its assumptions. Notes: There are three key assumptions for the MR study. Assumption 1: the genetic variants (GVs) selected as instrumental variables (IVs) should be robustly associated with the exposure; Assumption 2: the used IVs should not be associated with any potential confounder; Assumption 3: the GVs should influence the outcome risk merely through the exposures, not via any alternative pathway. Abbreviations: GVs = genetic variants; IV = instrumental variable; IVW = inverse variance weighted; MR = Mendelian randomization; MVMR = multivariable Mendelian randomization; SNP = single-nucleotide polymorphism; UVMR = univariable Mendelian randomization; WM = weighted median.
Fig. 2
Fig. 2
The overall framework of the proposed method Notes: The total effect of OLP on OCC, β3, was derived using univariable MR (i.e. genetically predicted OLP as exposure and OCC as outcome). The indirect effect using a two-step approach (where β1 is the total effect of OLP on IL-13, and β2 is the effect of IL-13 on OCC adjusting for exposure) and the product method (β1 × β2). Proportion mediated was the indirect effect divided by the total effect (β1 × β2/β3). Abbreviations: OLP = oral lichen planus; OL = oral leukoplakia; OCC = oral cavity cancer; IL-13 = interleukin-13; IL-9 = interleukin-9; IVW = inverse variance weighted; SNP = single-nucleotide polymorphism.
Figure 3
Figure 3
UVMR analysis of the causal effects of OLP on 41 inflammatory cytokines Notes: Association between genetically predicted OLP and 41 infammatory cytokines, using inverse variance weighted as the primary analytical method. OLP = oral lichen planus; CI = confidence interval; OR = odds ratio.
Figure 4
Figure 4
UVMR analysis of the causal effects of OLP-driven inflammatory cytokines on OCC Notes: Association between genetically predicted OLP-driven inflammatory cytokines and OCC, using inverse variance weighted as the primary analytical method. OLP = oral lichen planus; OCC = oral cavity cancer; CI = confidence interval; OR = odds ratio;IL-13 = interleukin-13; IL-9 = interleukin-9
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