加强食管癌不同阶段的治疗选择并提高患者生存率取决于及时、准确的诊断。血液代谢物可能在引起或预防食道癌方面发挥作用，但需要进一步研究以确定血液代谢物是否构成该疾病的遗传风险因素。为了解决这些问题，我们使用两样本孟德尔随机化 (MR) 研究评估了食道癌与 486 种血液代谢物之间的因果关系，这些代谢物充当遗传代理。我们利用两样本 MR 分析来评估血液之间的因果关系代谢物和食道癌。为了进行暴露，我们使用了 486 种代谢物的全基因组关联研究 (GWAS)，以及 Sakaue 等人针对食管癌的 GWAS 研究。用于初步分析。因果分析以随机逆方差加权（IVW）为主要方法，辅以MR-Egger和加权中位数（WM）分析。敏感性分析包括 MR-Egger 截距检验、Cochran Q 检验、MR-PRESSO 和留一分析。此外，还利用独立的食管癌 GWAS 数据进行复制和荟萃分析。 FDR 校正用于识别具有因果关系的特征。为了确定代谢物的结论，我们进行了 Steiger 检验、连锁不平衡评分回归和共定位分析。此外，我们利用MetaboAnalyst 5.0程序来分析代谢途径。这项研究发现食管癌与三种代谢物之间存在重要关联：1-亚油酰基甘油磷酸乙醇胺* [比值比 (OR) = 3.21，95% 置信区间 (CI)：1.42-7.26 ，p < 0.01]、焦谷氨酰胺*（OR = 1.92，95% CI：1.17-3.17，p < 0.01）和月桂酸（12:0）（OR = 3.06，95% CI：1.38-6.78，p < 0.01） .这项研究建立了三种确定的血液代谢物与食管癌之间的因果关系，为其发病机制提供了新的见解。版权所有 © 2024 Jia、Yi、Ma、Xu、Ou、Kong 和 Jia。

Enhancing therapy choices for varying stages of esophageal cancer and improving patient survival depend on timely and precise diagnosis. Blood metabolites may play a role in either causing or preventing esophageal cancer, but further research is needed to determine whether blood metabolites constitute a genetic risk factor for the disease. In order to tackle these problems, we evaluated the causal association between esophageal cancer and 486 blood metabolites that functioned as genetic proxies using a two-sample Mendelian randomization (MR) study.We utilized two-sample MR analyses to evaluate the causal links between blood metabolites and esophageal cancer. For the exposure, we used a genome-wide association study (GWAS) of 486 metabolites, and a GWAS study on esophageal cancer from Sakaue et al. was used for preliminary analyses. Causal analyses employed randomized inverse variance weighted (IVW) as the main method, supplemented by MR-Egger and weighted median (WM) analyses. Sensitivity analyses included the MR-Egger intercept test, Cochran Q test, MR-PRESSO, and leave-one-out analysis. Additionally, independent esophageal cancer GWAS data were utilized for replication and meta-analysis. FDR correction was applied to discern features with causal relationships. For conclusive metabolite identification, we conducted Steiger tests, linkage disequilibrium score regression, and colocalization analyses. Moreover, we utilized the program MetaboAnalyst 5.0 to analyze metabolic pathways.This study found an important association between esophageal cancer and three metabolites: 1-linoleoylglycerophosphoethanolamine* [odds ratio (OR) = 3.21, 95% confidence interval (CI): 1.42-7.26, p < 0.01], pyroglutamine* (OR = 1.92, 95% CI: 1.17-3.17, p < 0.01), and laurate (12:0) (OR = 3.06, 95% CI: 1.38-6.78, p < 0.01).This study establishes a causal link between three defined blood metabolites and esophageal cancer, offering fresh insights into its pathogenesis.Copyright © 2024 Jia, Yi, Ma, Xu, Ou, Kong and Jia.