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ORIGINAL RESEARCH ARTICLE

Autoimmune thyroiditis and pan-cancer risk: A comprehensive Mendelian randomization study

Cheng Qu1 ,  Bo Jiang1 ,  Chen Zhang1 ,  Chaoyu Jiang1 ,  Yanxue Wang1 ,  Lei Su1* ,  Yuqian Luo2*
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1 Department of Thyroid Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
2 Clinical Medicine Research Center, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China
EJMO, 025230245 https://doi.org/10.36922/EJMO025230245
Received: 5 June 2025 | Revised: 12 July 2025 | Accepted: 1 September 2025 | Published online: 10 October 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: Autoimmune thyroiditis (AIT), clinically termed Hashimoto’s thyroiditis (HT), is a chronic autoimmune condition characterized by progressive immune-mediated degeneration of thyroid tissue. The association between AIT and cancer risk, particularly thyroid cancer, remains controversial.

Objective: This study is aimed to investigate potential causal associations between AIT/HT and thyroid cancers or extra-thyroidal cancers comprehensively.

Methods: To clarify this uncertainty, we employed Mendelian randomization (MR) analysis to evaluate causal associations between genetic predisposition to AIT and pan-cancer risk, including subtypes of thyroid cancer and extra-thyroidal malignancies. Summary statistics were pooled from comprehensive genome-wide studies, including two independent AIT/HT datasets, 10 thyroid neoplasm datasets, and 33 extra-thyroidal cancer datasets. Bidirectional two-sample MR analyses were conducted to mitigate confounding and reverse causation. Quality control was reinforced through sensitivity analyses.

Results: Contrary to previous observational studies, our study found no genetically supported causal link between AIT/HT and the development of thyroid carcinoma. However, elevated risks of non-Hodgkin lymphoma, primary lymphoid/hematopoietic malignancies, testicular cancer, and brain cancer might be associated with AIT/HT. Sensitivity analyses confirmed the robustness of these results, although some associations exhibited heterogeneity or pleiotropy.

Conclusion: These findings reveal tissue-specific effects of thyroid autoimmunity on cancer development, suggesting distinct biological pathways beyond thyroid malignancies. This study provides genetic evidence that refines cancer risk assessment in patients with AIT/HT and emphasizes the need for further mechanistic research to elucidate underlying biological processes.

Keywords
Autoimmune thyroiditis
Mendelian randomization analysis
Thyroid cancer
Pan-cancer risk
Hashimoto’s thyroiditis
Funding
This work was supported by the National Natural Science Foundation of China (grant no. #81900712) and the Project of the Institute of Chinese Medicine, Nanjing University (grant no. #ICM2024013).
Conflict of interest
The authors declare that they have no competing interests.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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