基于生活方式与肝胆恶性肿瘤发生发展因果关系的孟德尔随机化研究  

Mendelian randomization study based on relationship between lifestyle and occurrence and development of hepatobiliary malignancies

作　　者：刘华青 陈庆凯 陈永新 邱润昊 丁绪鹏 宋奉京 王岩[1] 王葆林 曹宏[1] LIU Huaqing;CHEN Qingkai;CHEN Yongxin;QIU Runhao;DING Xupeng;SONG Fengjing;WANG Yan;WANG Baolin;CAO Hong(Department of General Surgery,Xinmin District,China-Janpan Union Hospital,Jilin University,Changchun 130021,China)

机构地区：[1]吉林大学中日联谊医院新民院区普通外科,吉林长春130021

出　　处：《吉林大学学报（医学版）》2024年第3期778-785,共8页Journal of Jilin University：Medicine Edition

基　　金：吉林省教育厅科学技术研究项目(JJKH20211062KJ)。

摘　　要：目的:探讨使用孟德尔随机化研究方法分析生活方式与肝胆恶性肿瘤发生发展的因果关系,为肝胆恶性肿瘤预防和治疗提供潜在临床证据。方法:纳入相互独立的大规模全基因组关联研究(GWAS)汇总数据,设定七步纳入标准进行工具变量筛选。暴露的生活方式包括饮食中碳水化合物摄入百分率、脂肪摄入百分率、蛋白质摄入百分率、咖啡摄入量、每周饮酒次数、闲暇时电子屏幕接触时间、闲暇时中高强度体育运动(MVPA)、工作时的久坐行为、首次吸烟年龄、每日吸烟数量、目前吸烟状态和既往吸烟状态共12种表型。采用逆方差加权法(IVW)的随机效应模型作为主分析方法,采用Cochrane's Q检验评估异质性,采用MR-Egger截距法检验水平多效性。结果:目前吸烟状态与易患肝外胆管癌呈显著因果关系(OR=1.607,95%CI:1.113~2.322,P=0.011)。咖啡摄入量较高与患肝癌及肝内胆管癌的较高风险有显著因果关系(OR=1.000,95%CI:0.999~1.000,P=0.012)。在体育活动中,较多的MVPA与患肝癌及肝内胆管癌的较低风险具有显著因果关系(OR=0.998,95%CI:0.996~0.999,P=0.002)。Cochrane’s Q检验提示MVPA与肝外胆管癌(Q=18.354,P=0.049)和蛋白质摄入百分率与肝癌及肝内胆管癌(Q=12.715,P=0.026)具有轻度异质性,MR-Egger截距法显示本研究无水平多效性。结论:目前吸烟状态与患肝外胆管癌的高风险具有因果关系,较多的MVPA与患肝癌及肝内胆管癌的较低风险具有因果关系。对患者进行适当的戒烟劝导和体育运动教育可能会为预防肝胆恶性肿瘤提供潜在益处。Objective:To analyze the causal relationship between lifestyle-based factors and the occurrence and development of hepatobiliary malignancies by Mendelian randomization study method,and to provide the potential clinical evidence for the prevention and treatment of hepatobiliary malignancies.Methods:The data from large-scale,independent genome-wide association studies(GWAS) were selected,and seven-step inclusion criteria for the instrumental variable screening were set up.The exposure lifestyles included the percentage of carbohydrate intake,percentage of fat intake,percentage of protein intake in the diet,coffee intake,weekly alcohol consumption times,leisure electronic screen exposure time,moderate to vigorous intensity physical activity(MVPA) during leisure time,sedentary behavior at work,age at first smoking,daily smoking quantity,current smoking status,and past smoking status,totaling 12 phenotypes.The primary analysis method used was the random effect model of the inverse variance weighted(IVW) method,and the heterogeneity was detected by Cochrane's Q test and the horizontal pleiotropy was detected by MR-Egger intercept method.Results:The current smoking status was significantly positively correlated with the increasing risk of extrahepatic cholangiocarcinoma(OR=1.607,95% CI:1.113-2.322,P=0.011).Higher coffee intake was causally linked to a higher risk of liver cancer and intrahepatic cholangiocarcinoma(OR=1.000,95% CI:0.999-1.000,P=0.012).In the physical activity,more MVPA was associated with the lower risk of liver cancer and intrahepatic cholangiocarcinoma(OR=0.998,95% CI:0.996-0.999,P=0.002).The Cochrane's Q test results showed that there was mild heterogeneity between MVPA and extrahepatic cholangiocarcinoma(Q=18.354,P=0.049) as well as the percentage of protein intake and intraphepatic cholangiocarainoma(Q=12.715,P=0.026),and the MR-Egger intercept method results showed there was no horizontal pleiotropy.Conclusion:There is a causal relationship between current smoking status and extrahepatic cholangio

关 键 词：生活方式 肝内胆管肿瘤 胆管肿瘤 肝肿瘤 孟德尔随机化研究 

分 类 号：R735[医药卫生—肿瘤]