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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Thyroid Endocrinology
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1411629
This article is part of the Research Topic Thyroid Hormone Actions in Cancer, volume II View all articles

Causal association between hyperthyroidism and risk of gastroesophageal reflux or esophageal cancer: A bidirectional Mendelian randomization Investigation

Provisionally accepted
Xingyu Zhu Xingyu Zhu 1,2Ming Li Ming Li 1,2*Hanghang Gan Hanghang Gan 1,2*Yingqiang Guo Yingqiang Guo 2*
  • 1 West China Hospital, Sichuan University, Chengdu, China
  • 2 Department of Cardiovascular surgery, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China

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

    Emerging observational studies indicated an association between hyperthyroidism and gastrointestinal disorders. However, it remains unclear whether this association is causal, particularly in the case of gastroesophageal reflux (GERD) and esophageal cancer.To assess the potential causal relationship between hyperthyroidism and GERD or esophageal cancer, we conducted a bidirectional 2-sample Mendelian randomization study. Independent genetic instruments for hyperthyroidism from the UK Biobank (N case=3,545 and N control=459,388) and public genome-wide association study (GWAS) dataset (N case=3,731 and N control=480,867) were used to investigate the association with esophageal cancer in the UK Biobank study (N case=740 and N control=372,016) and GERD in the public GWAS database (N case=20,381 and N control=464,217). Four different approaches (inverse variance weighted (IVW), weighted mode, MR-Egger, and weighted median regression) were used to ensure that our results more reliable.Additional sensitivity analyses were also performed to validate our results.When hyperthyroidism was considered as the exposure factor, it appeared to act as a protective factor for GERD (ORIVW = 0.88, 95% CI, 0.79-0.99, P = 0.039), while as a risk factor for esophageal cancer (ORIVW = 1.03, 95% CI, 1.01-1.06, P = 0.003).However, there is no evidence supporting a reverse causal relationship between genetic susceptibility to hyperthyroidism and GERD or esophageal cancer.Our findings provided genetic evidence supporting bidirectional causal relationships between hyperthyroidism and GERD or esophageal cancer. These results substantiate certain discoveries from previous observational studies on a causal level and provide insight into relevant genetic susceptibility factors.

    Keywords: Hyperthyroidism, esophageal cancer, Gastroesophageal Reflux, Mendelian randomization, European ancestry

    Received: 03 Apr 2024; Accepted: 29 Aug 2024.

    Copyright: © 2024 Zhu, Li, Gan and Guo. 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:
    Ming Li, Department of Cardiovascular surgery, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China
    Hanghang Gan, Department of Cardiovascular surgery, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China
    Yingqiang Guo, Department of Cardiovascular surgery, West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China

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