山西医科大学学报2025，Vol.56Issue(2)：113-120,8.DOI:10.13753/j.issn.1007-6611.2025.02.001
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
摘要
Abstract
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 linoleic acid to total fatty acids,the ratio of 18∶2 linoleic acid to total fatty acids,the ratio of phospholipids to total lipids in high-density lipoprotein particles,and tyro-sine level are identified as protective factors against prostate cancer.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Key words
circulating metabolic biomarkers/prostate cancer/Mendelian randomization/causal relationship/lipopro-tein/lipid/genome-wide association studies分类
医药卫生引用本文复制引用
徐新宇,梁文浩,彭煜,朱文静,刘治,刘彦飞,张杰,王韬毓,钟琪,徐静..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[J].山西医科大学学报,2025,56(2):113-120,8.基金项目
国家自然科学基金资助项目(82174451) （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) （JHXM-2021018）
中医优势专科建设专项项目[YW(2023-2024)-01-04] （2023-2024）
