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ORIGINAL RESEARCH article

Front. Mol. Biosci.
Sec. Metabolomics
Volume 11 - 2024 | doi: 10.3389/fmolb.2024.1391419
This article is part of the Research Topic Metabolomics in Personalized Cancer Medicine View all articles

Genetically predicted 486 blood metabolites in relation to risk of esophageal cancer: A Mendelian randomization study

Provisionally accepted
Caiyan Jia Caiyan Jia 1,2*Dan Yi Dan Yi 1*Mingze Ma Mingze Ma 1*Qian Xu Qian Xu 1Yan Ou Yan Ou 1*Fanming Kong Fanming Kong 1Yingjie Jia Yingjie Jia 1
  • 1 First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Nankai District, China
  • 2 First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China

The final, formatted version of the article will be published soon.

    Background and Objective: 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.Results: 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 3 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.

    Keywords: Mendelian randomization, Blood metabolites, Colocalization analysis, snps, esophageal cancer Mendelian randomization, esophageal cancer

    Received: 25 Feb 2024; Accepted: 16 Sep 2024.

    Copyright: © 2024 Jia, Yi, Ma, Xu, Ou, Kong and Jia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Caiyan Jia, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Nankai District, China
    Dan Yi, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Nankai District, China
    Mingze Ma, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Nankai District, China
    Yan Ou, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Nankai District, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.