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ORIGINAL RESEARCH article

Front. Genet.
Sec. Cancer Genetics and Oncogenomics
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1446661
This article is part of the Research Topic Emerging Relevance of Molecular Profiling in Global Cancer Research and Management View all 4 articles

Mendelian Randomization and multiomics comprehensively reveal the causal relationship and potential mechanism between atrial fibrillation and gastric cancer

Provisionally accepted
Jingcheng Zhang Jingcheng Zhang 1,2Shuo Zhang Shuo Zhang 1,2Sicheng Zhao Sicheng Zhao 1,2Jiaheng Lou Jiaheng Lou 1,2Zhiyuan Song Zhiyuan Song 1,2Xing Bai Xing Bai 1,2Yan Cai Yan Cai 1,2Tao Jiang Tao Jiang 1,2*Guangji Zhang Guangji Zhang 1,2*
  • 1 School of Basic Medical Sciences, Zhejiang Chinese Medical University, zhejiang Hangzhou, China
  • 2 Key Labortary of Blood-stasis-toxin Syndrome of Zhejiang Province, Zhejiang, China

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

    Using a two-sample Mendelian Randomization method, this study revealed the potential causal effect of atrial fibrillation(AF) on gastric cancer(GC) risk by constructing a genetic instrument containing 136 AF associated SNPs. The results showed that AF was negatively associated with gastric cancer, and further analysis revealed that this relationship was independent of GC risk factors such as chronic gastritis, Helicobacter pylori infection, and alcohol consumption. Subsequently, analysis identifies 62 AF-GC co-associated genes and constructs a protein-protein interaction network of key genes. Enrichment analysis reveals associations of these genes with pathways related to cardiovascular disease, inflammatory gastrointestinal diseases, and tumorigenesis. Through single-cell sequencing data analysis, fibroblast subpopulations associated with the key gene set are identified in GC, showing significant correlations with cancer progression and inflammation regulation pathways.Transcription factor analysis and developmental trajectory analysis reveal the potential role of fibroblasts in GC development. Finally, prognosis analysis and gene mutation analysis using TCGA-STAD data indicate an adverse prognosis associated with the key gene set in GC. This study provides new insights into the association between AF and GC and offers novel clues for understanding its impact on the pathogenesis and therapeutic strategies of GC.

    Keywords: Atrial Fibrillation, gastric cancer, Genetic instrument, Mendelian randomization, single-cell sequencing, Fibroblasts

    Received: 10 Jun 2024; Accepted: 13 Jan 2025.

    Copyright: © 2025 Zhang, Zhang, Zhao, Lou, Song, Bai, Cai, Jiang and Zhang. 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:
    Tao Jiang, School of Basic Medical Sciences, Zhejiang Chinese Medical University, zhejiang Hangzhou, China
    Guangji Zhang, School of Basic Medical Sciences, Zhejiang Chinese Medical University, zhejiang Hangzhou, 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.