摘要
目的 探究全身炎症因子与肝癌发生风险之间的因果关系.方法 本研究基于公开的全基因组关联研究(genome-wide association study,GWAS)数据库,以41个全身炎症因子为暴露因素,数据来源于一项样本量为8 293人的芬兰研究;以肝癌为结局变量,数据来源于芬兰数据库(FINNGen).分别采用逆方差加权法(inverse variance weighted,IVW)、MR-Egger、加权中位数(weighted median estimator,WME)、加权模式法(weighted mode,WM)进行两样本孟德尔随机化分析,采用MR-Egger回归进行多效性分析,利用Cochran's Q检验进行异质性分析,采用"留一法"进行敏感性分析.结果 两样本孟德尔随机化分析的IVW法结果显示,肿瘤坏死因子相关凋亡诱导配体(TNF-related apoptosis-inducing ligand,TRAIL)水平(0R=0.77,95％CI:0.61～0.97,P=0.025)、巨噬细胞集落刺激因子(macrophage-stimulating factor,MCSF)水平(OR=0.69,95％CI:0.50～0.95,P=0.024)和白细胞介素-18(interleukin-18,IL-18)水平(OR=0.77,95％CI:0.61～0.97,P=0.026)与肝癌发生风险呈负相关关系.结论 TRAIL、IL-18、MCSF与肝癌存在潜在的负向因果关联,可能为肝癌的保护因素.
Abstract
Objective To explore the causal relationship between systemic inflammatory factors and the risk of hepatocellular carcinoma.Methods This study was based on the published genome-wide association study(GWAS)database.The exposure factor was 41 systemic inflammatory regulators.The data were derived from a Finland study with a sample size of 8 293 people.The outcome variable was hepatocellular carcinoma,which was derived from the Finnish database(FINNGen).Two-sample Mendelian randomization analysis was performed using inverse variance weighted(IVW),MR-Egger,weighted median estimator(WME),and weighted mode(WM)MR-Egger was carried out for pleiotropy analysis,Cochran's Q test was used for heterogeneity analysis,and leave-one-out method was used for sensitivity analysis.Results IVW results of two-sample Mendelian randomization analysis showed that TNF-related apoptosis-inducing ligand(TRAIL)level(OR=0.77,95％CI=0.61-0.97,P=0.025),macrophage-stimulating factor(MCSF)level(OR=0.69,95％CI=0.50-0.95,P=0.024)and interleukin-18(IL-18)level(OR=0.77,95％CI=0.61-0.97,P=0.026)were negatively correlated with the risk of hepatocellular carcinoma.Conclusion TRAIL,IL-18 and MCSF had potential negative causal association with hepatocellular carcinoma,which migh be protective factors for hepatocellular carcinoma.
基金项目
湖南省教育厅优秀青年项目(23B0392)
湖南省中医药科研课题一般项目(B2023010)
湖南中医药大学2023年度大学本科生科研创新基金项目(2023BKS116)
湖南中医药大学校级科研项目(Z2023YYJJ08)
NETL
NSTL
万方数据