循环代谢生物标志物与前列腺癌因果关系的双向孟德尔随机化研究  

Bidirectional Mendelian randomization study on causal relationship between circulating metabolic biomarkers and prostate cancer

作　　者：徐新宇 彭煜[1] 朱文静[1] 刘治 刘彦飞 张杰[1] 王韬毓 钟琪 徐静[1] 梁文浩 XU Xinyu;PENG Yu;ZHU Wenjing;LIU Zhi;LIU Yanfei;ZHANG Jie;WANG Taoyu;ZHONG Qi;XU Jing;LIANG Wenhao(Department of Urology,Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China)

机构地区：[1]上海中医药大学附属岳阳中西医结合医院泌尿外科,上海200437

出　　处：《山西医科大学学报》2025年第2期113-120,共8页Journal of Shanxi Medical University

基　　金：国家自然科学基金资助项目(82174451);上海吴孟超医学科技基金会临床医学基础与应用研究专项基金项目(JHXM-2021018);中医优势专科建设专项项目[YW(2023-2024)-01-04]。

摘　　要：目的 采用两样本孟德尔随机化方法研究233种循环代谢生物标志物与前列腺癌的因果关系。方法 利用全基因组关联研究数据(genome-wide association studies,GWAS),暴露因素为233种循环代谢生物标志物,结局变量为前列腺癌。采用逆方差加权(inverse variance weighted,IVW)法、加权中位数(weighted median,WM)法、MR-Egger回归、加权模式和简单模式研究暴露与结局的因果关系,其中以IVW作为主要分析方法,并进行敏感性分析以检验结果可靠性。结果 根据IVW的统计结果,有2种标志物与前列腺癌的发生风险呈正向因果关联:小低密度脂蛋白中甘油三酯与总脂质的比值(P=0.042),乳糜微粒和极大VLDL中总胆固醇与总脂质的比值(P=0.042)。有4种标志物与前列腺癌呈现负向因果关联:高密度脂蛋白中磷脂与总脂质的比值(P=0.025),共轭亚油酸与总脂肪酸的比值(P=0.009),亚油酸与总脂肪酸的比例为18∶2(P=0.045),酪氨酸水平(P=0.045)。其他4种方法的统计结果与IVW不完全一致(多数P>0.05),但5种方法的因果效应方向基本一致,结果仍旧可靠。敏感性分析未发现异质性和多效性,表明结果稳健。反向MR分析未发现前列腺癌能够影响6种循环代谢生物标志物水平。结论 233种循环代谢生物标志物中,小低密度脂蛋白中甘油三酯与总脂质的比值、乳糜微粒和极大VLDL中总胆固醇与总脂质的比值是前列腺癌的危险因素,共轭亚油酸与总脂肪酸的比值、亚油酸与总脂肪酸的比例为18∶2、高密度脂蛋白中磷脂与总脂质的比值、酪氨酸水平是前列腺癌的保护因素。Objective To investigate the causal relationship between 233 circulating metabolic biomarkers and prostate cancer by a two-sample Mendelian randomization(MR)approach.Methods Based on the data from genome-wide association studies(GWAS),the causal relationships between exposure factors(233 circulating metabolic biomarkers)and outcome(prostate cancer)were analyzed using inverse variance weighted(IVW),weighted median(WM),MR-Egger regression,weighted mode,and simple mode methods.Among them,IVW was used as the primary analysis method.Sensitivity analysis was conducted to assess the reliability of the results.Results Based on the IVW results,two circulating metabolic biomarkers showed a positive causal association with prostate cancer risk:the ratio of triglycerides to total lipids in small LDL particles(P=0.042)and the ratio of total cholesterol to total lipids in chylomi-crons and extremely large VLDL particles(P=0.042).Four biomarkers exhibited a negative causal association with prostate cancer:the ratio of phospholipids to total lipids in high-density lipoprotein particles(P=0.025),the ratio of conjugated linoleic acid to total fatty acids(P=0.009),the ratio of 18∶2 linoleic acid to total fatty acids(P=0.045),and tyrosine level(P=0.045).The statistical results of the other four methods(most P>0.05)were not entirely consistent with those of the IVW method,but the causal effect direc-tions of the five methods were generally consistent,indicating that the results were reliable.The sensitivity analysis revealed no hetero-geneity or pleiotropy,indicating that the findings were robust.Inverse MR analysis did not find evidence that prostate cancer influ-enced the levels of six circulating metabolic biomarkers.Conclusion Among the 233 circulating metabolic biomarkers,the ratio of triglycerides to total lipids in small LDL particles and the ratio of total cholesterol to total lipids in chylomicrons and extremely large VLDL particles are identified as risk factors for prostate cancer.Conversely,the ratio of conjugated linol

关 键 词：循环代谢生物标志物 前列腺癌 孟德尔随机化 因果关系 脂蛋白 脂质 全基因组关联研究 

分 类 号：R737.25[医药卫生—肿瘤]