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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1410994
This article is part of the Research Topic The Interplay between Immuno-Inflammatory Response and Oxidative Stress in Cancer Pathogenesis View all articles

Genetically predicted Caspase 8 levels mediates the causal association between CD4+ T cell and breast cancer

Provisionally accepted
Yanbin Chen Yanbin Chen 1Zequn Zheng Zequn Zheng 1Xifeng Huang Xifeng Huang 1Lei Xie Lei Xie 2*Jinhong Wang Jinhong Wang 1
  • 1 Other, Shantou, China
  • 2 First Affiliated Hospital of Shantou University Medical College, Shantou, China

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

    Background: Breast cancer (BC) remains a significant contributor to female mortality globally, with inflammation and the immune system implicated in its pathogenesis. To elucidate potential causal relationships, we evaluated the relationship among 731 immune cell phenotypes and BC be at risk by using Mendelian randomization (MR), while also exploring inflammatory proteins as mediators in this association.: We obtained immune cell genome-wide association study (GWAS) summary data. (Study ID: GCST0001391 to GCST0002121) and 91 inflammatory factors (Study ID: GCST90274758 to GCST90274848) from the GWAS Catalog. Additionally, the source of BC GWAS data was obtained from the IEU Open GWAS project. (ukb-b-16890 for discovery and GCST004988 for validation). We investigated the causal link between immune cells and BC risk by employing a twosample Mendelian randomization (MR) method. Furthermore, we use a two-step MR to quantify the percentage of mediation of immune cell-BC causal effects mediated by inflammatory proteins. In addition, to ensure the robustness of immune cell-BC causal effects, we utilized another BC GWAS database (GCST004988) for validation. To make sure the causal findings were robust, a sensitivity analysis was done. Results: In both discovery and validation GWAS, Aa critical inverse correlation among between CD4+ T cells and BC risk was found using MR analysis. (Discovery: OR, 0.996; P = 0.030. Validation: OR, 0.843; P = 4.09E-07) , with with Caspase 8 levels mediating 18.9% of the reduced BC risk associated with immune cells. (Mediation proportion=a×b/c, Discovery:0.151×-0.005/-0.004=18.9%; Validation:0.151×-0.214/-0.171=18.9%) 设置了格式: 字体: 小四, 字体颜色: 自动设置 Conclusion: Our study establishes a causal connection linking among CD4+ T cells and BC, with Caspase 8 levels partially mediating this relationship. These findings enhance our genetic and molecular comprehension of BC, suggesting potential pathways for future BC immunotherapy drug development.

    Keywords: breast cancer, CD4+T cell, Caspase 8 levels, Mendelian randomization, immune cell

    Received: 02 Apr 2024; Accepted: 13 Sep 2024.

    Copyright: © 2024 Chen, Zheng, Huang, Xie and Wang. 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: Lei Xie, First Affiliated Hospital of Shantou University Medical College, Shantou, 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.