胰岛素样生长因子1与结直肠癌因果关系的两样本孟德尔随机化研究  

Two sample Mendelian randomization study on causal relationship between insulin-like growth factor-1 and colorectal cancer

作　　者：穆华夏 卜伟晓 丁淑婷 高梦瑶 苏维强 张震 薄其付 刘峰 石福艳 王清华 孔雨佳 王素珍 MU Huaxia;BU Weixiao;DING Shuting;GAO Mengyao;SU Weiqiang;ZHANG Zhen;BO Qifu;LIU Feng;SHI Fuyan;WANG Qinghua;KONG Yujia;WANG Suzhen(Department of Health Statistics,School of Public Health,Shandong Second Medical University,Weifang 261053,China;Department of Oncology,Affiliated Hospital,Shandong Second Medical University,Weifang 261041,China)

机构地区：[1]山东第二医科大学公共卫生学院卫生统计学教研室,山东潍坊261053 [2]山东第二医科大学附属医院肿瘤科,山东潍坊261041

出　　处：《吉林大学学报(医学版)》2025年第2期479-485,共7页Journal of Jilin University:Medicine Edition

基　　金：国家自然科学基金青年项目(82003560);山东省科技厅自然科学基金面上项目(ZR2020MH340,ZR2023MH313);陕西省科技厅科技计划项目(2024SF-YBXM-256);山东省教育厅大学生创新创业基金项目(S202410438047);山东第二医科大学大学生创新创业基金项目(X2024374,X2024394)。

摘　　要：目的:基于双向两样本孟德尔随机化(MR)分析,探索胰岛素样生长因子1(IGF-1)与结直肠癌(CRC)之间的因果关联。方法:基于已公开的全基因组关联研究(IEU OpenGWAS)项目的公开汇总数据进行双向两样本MR分析,采用逆方差加权法(IVW)作为主要分析方法,采用加权中位数法(WM)、MR-Egger回归法、加权众数法(WME)和简单众数法(SM)进行辅助分析,以评估IGF-1对CRC的因果影响;通过敏感性分析检查结果的稳健性。结果:以IGF-1作为暴露因素共筛选到386个单核苷酸多态性(SNPs)作为工具变量(IVs)。MR分析,IGF-1与CRC之间存在正向因果关联,比值比(OR)为1.178,95%置信区间(CI)为1.092~1.272,P<0.001;且该因果关联在校正了身高后仍然存在[OR(95%CI)=1.214(1.111,1.327),P<0.001]。Cochran's Q检验显示IV之间存在异质性(P<0.05),MR-Egger回归法未发现IV的水平多效性(P>0.05)。留一法逐个剔除SNPs后,结果显示该因果关联稳健。反向MR分析显示IGF-1与CRC之间不存在反向因果关系[OR(95%CI)=1.017(0.997,1.037),P=0.103]。结论:IGF-1水平与CRC之间存在因果关联,高IGF-1水平是CRC的潜在风险因素。Objective:To explore the causal association between insulin-like growth factor-1(IGF-1)and colorectal cancer(CRC)based on two sample Mendelian randomization(MR)analysis.Methods:A bidirectional two sample MR analysis was conducted based on publicly aggregated data from the IEU OpenGWAS project.The inverse variance weighted(IVW)method was used as the main analysis model to assess the causal relationship between IGF-1 and CRC.Additional analyses were performed using weighted median(WM),MR-Egger regression,weighted mode estimator(WME),and simple mode(SM)methods.Sensitivity analysis was performed to assess the robustness of the results.Results:A total of 386 single nucleotide polymorphisms(SNPs)were selected as instrumental variables(IVs)with IGF-1 as the exposure factor.The MR analysis results revealed a positive causal association between IGF-1 and the risk of CRC[odds ratio(OR)=1.178,95%confidence interval(CI):(1.092-1.272)](P<0.001),and the association remained significant after adjusting for height[OR(95%CI)=1.214(1.111,1.327)](P<0.001).Cochran’s Q-test showed heterogeneity among the IVs(P<0.05),while the horizontal pleiotropy of IV was not detected by the MR-Egger regression(P>0.05).The leave-one-out analysis showed that the MR results were robust.Reverse MR analysis indicated no reverse causal relationship between IGF-1 and CRC[OR(95%CI):1.017(0.997,1.037)](P=0.103).Conclusion:There is a causal relationship between IGF-1 level and CRC,and elevated IGF-1 level could be a risk factor for CRC.

关 键 词：胰岛素样生长因子1 结直肠癌 孟德尔随机化 身高 单核苷酸多态性 

分 类 号：R735.3[医药卫生—肿瘤]