肝胆胰外科杂志2025，Vol.37Issue(10)：674-681,8.DOI:10.11952/j.issn.1007-1954.2025.10.004
基于孟德尔随机化分析血管内皮生长因子水平与胰腺癌的因果关系
Mendelian randomization study on causal association of vascular endothelial growth factor levels with pancreatic cancer
蒋汉林 1纽维桥 1杨光 1潘雨佳 1黄立宁 1吴建武 1蒋新卫1
作者信息
- 1. 南京医科大学附属苏州市立医院肝胆胰外科,江苏苏州 215000
- 折叠
摘要
Abstract
Objective This study investigates the causal relationship between VEGF levels and pancreatic cancer with Mendelian randomization(MR)analysis.Methods A two-sample MR analysis was conducted.Genome-wide association study(GWAS)data was used to extract genetic instrumental variables(IVs)which reveal significantly association between VEGF levels and pancreatic cancer(P＜1×10-5).VEGF levels were set as the exposure factor,and pancreatic cancer as the outcome.Parameters for linkage disequilibrium(LD)removal were set at r2＜0.001 and a genetic distance kb＞10,000.Causal relationships were analyzed by inverse variance weighted(IVW),MR-Egger,weighted median(WM),simple mode,and weighted mode methods.Heterogeneity was assessed via Cochran's Q statistics(MR-Egger and IVW),while pleiotropy was evaluated by MR-Egger intercept and MR-PRESSO(Mendelian Randomization Pleiotropy Residual Sum and Outlier test,MR-PRESSO).Leave-one-out analysis was performed to confirm the stability of results.Results Elevated VEGF levels which genetically predicted were significantly associated with an increased risk of pancreatic cancer(OR=1.15,95％CI 1.01 to 1.30,P=2.933×10-2).MR-Egger,WM,simple mode,and weighted mode analyses consistently indicated a positive correlation(OR＞1).Cochran's Q tests(IVW and MR-Egger)revealed no heterogeneity(P＞0.05),and MR-Egger intercept and MR-PRESSO confirmed no horizontal pleiotropy(P＞0.05).Leave-one-out analysis demonstrated robust stability of the results.Conclusion VEGF levels may represent a causal risk factor for pancreatic cancer,suggesting that targeting the VEGF signaling pathway could be a potential therapeutic strategy.关键词
血管内皮生长因子/胰腺癌/孟德尔随机化/遗传学/因果关系Key words
vascular endothelial growth factor/pancreatic cancer/Mendelian randomization/genetics/casual association分类
临床医学引用本文复制引用
蒋汉林,纽维桥,杨光,潘雨佳,黄立宁,吴建武,蒋新卫..基于孟德尔随机化分析血管内皮生长因子水平与胰腺癌的因果关系[J].肝胆胰外科杂志,2025,37(10):674-681,8.
