• Jieyin Deng, Silin Wu, Ye Huang, Yi Deng, and Ke Yu.
• Department of General Medical Practice, General Hospital of PLA Western Theater Command, Chengdu, China.
• Medicine (Baltimore). 2024 Oct 25; 103 (43): e40122e40122.

AbstractIt remains unclear what causes esophageal cancer (EC), but blood metabolites have been connected to it. Our study performed a Mendelian randomization (MR) analysis to assess the causality from genetically proxied 1400 blood metabolites to EC level. A two-sample MR analysis was employed to evaluate the causal relationship between 1400 blood metabolites and EC. Initially, the EC genome-wide association study (GWAS) data (from Jiang L et al) were examined, leading to the identification of certain metabolites. Subsequently, another set of EC GWAS data from FINNGEN was utilized to validate the findings. Causality was primarily determined through inverse variance weighting, with additional support from the MR-Egger, weighted median, and MR-PRESSO models. Heterogeneity was assessed using the MR Cochran Q test. The MR-Egger intercept and MR-PRESSO global methods were employed to detect multicollinearity. In this study, Bonferroni corrected P value was used for significance threshold. We found 2 metabolites with overlaps, which are lipids. Docosatrienoate (22:3n3) was found to be causally associated with a decreased risk of EC, as evidenced by the EC GWAS data (from Jiang et al) (odds ratio [OR] = 0.620, 95% confidence interval [CI] = 0.390-0.986, P = .044) and the EC GWAS data (from FINNGEN) (OR = 0.77, 95% CI = 0.6-0.99, P = .042), these results were consistent across both data sets. Another overlapping metabolite, glycosyl-N-(2-hydroxyneuramoyl)-sphingosine, was associated with the risk of ES, with EC GWAS data (from Jiang L et al) (OR = 1.536, 95% CI = 1.000-2.360, P = .049), while EC GWAS data (from FINNGEN) (OR = 0.733, 95% CI = 0.574-0.937, P = .013), the 2 data had opposite conclusions. The findings of this study indicate a potential association between lipid metabolites (Docosatrienoate (22:3n3) and glycosyl-N-(2-hydroxynervonoyl)-sphingosine (d18:1/24:1 (2OH))) and the risk of esophageal carcinogenesis.Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.

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