背景:虽然观察性研究和实验数据表明口腔扁平苔藓(OLP)与口腔癌(OCC)之间存在联系,因果关系和炎性细胞因子的作用尚不清楚.
方法:本研究采用单变量和多变量孟德尔随机化(MR)分析来研究OLP与OCC风险之间的因果关系。此外,探讨了炎性细胞因子在调节这种关联中的潜在作用.仪器变量来自FinngenR9数据集中与OLP相关的遗传变异(n=377,277),有41种炎性细胞因子作为潜在的介质,OCC(n=4,151)作为结果变量。分析方法包括方差加权反(IVW),加权中位数,MR-Egger,和MR-PRESSO用于评估OLP之间的因果关系,炎性细胞因子,和OCC风险。然后应用多变量MR(MVMR)来量化这些细胞因子在OLP和增加的OCC风险之间的关系中的介导作用。
结果:MR分析提供了OLP(OR=1.417,95%CI=1.167-1.721,p<0.001)与OCC风险之间存在因果关系的有力证据。此外,两种炎症细胞因子受OLP显著影响,IL-13(OR=1.088,95%CI:1.007-1.175,P=0.032)和IL-9(OR=1.085,95%CI:1.005-1.171,P=0.037),已确定。随后的分析显示,仅在IL-13(OR=1.408,95%CI:1.147-1.727,P=0.001)和更高的OCC风险之间存在显着因果关系。将其确立为潜在的调解人。Further,MVMR分析显示IL-13(OR=1.437,95%CI=1.139~1.815,P=0.002)介导OLP与OCC的关系,占调解的8.13%。
结论:这项研究不仅阐明了OLP与OCC风险之间的潜在因果关系,而且还强调了IL-13在这种关联中的关键中介作用。
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.
CONCLUSIONS: 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.