Abstract
Background
The effect of iodine deficiency, especially during the fetal period, on thyroid cancer risk remains unclear. The evidence from observational studies is controversial because of the inevitable confounding factors. We studied the causal effect of congenital iodine deficiency on differentiated thyroid cancer (DTC) based on Mendelian randomization (MR).
Methods
Two-Sample MR analysis was performed using data from published genome-wide association studies, including congenital iodine deficiency syndrome (CIDS) (353 cases, 187,684 controls) and DTC (649 cases, 431 controls) data.
Results
There was a causal relationship between CIDS and DTC (P < 0.05), with CIDS increasing the DTC risk by 37.4% (OR = 1.374, 95%CI = 1.110–1.700). Heterogeneity tests and tests of multiple validities indicated that the results were solid and reliable (all P < 0.05).
Conclusions
Fetal iodine deficiency increases the risk of DTC, so future clinical studies should focus on the effect of iodine supplementation during pregnancy to reduce the risk of thyroid cancer in the offspring.
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Data availability
The exposure data of congenital iodine-deficiency syndrome (https://gwas.mrcieu.ac.uk/datasets/finn-b-E4_CONGEIOD/) and the outcome data of thyroid cancer (https://gwas.mrcieu.ac.uk/datasets/ieu-a-1082/) is available.
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Acknowledgements
We want to acknowledge the participants and investigators of the FinnGen study for the available GWAS data of CIDS. We also want to acknowledge Aleksandra Köhler and other co-authors for the available GWAS data of DTC. This study was funded by Major Basic Research Project of Natural Science Foundation of Shandong Province (Grant No. ZR2020ZD15), the National Natural Science Foundation of China (Grant No. 82070800, 82270845), a Special fund for Taishan industrial leading talent project, and supported by Jinan Clinical Research Center for Endocrine and Metabolic Diseases.
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Conceptualization: X.H. and L.C. Data Curation: M.Y., Y.L. Formal analysis: K.L. and Q.Q. Project administration: P.L. Supervision: X.H. and L.C. Writing-original draft: K.L. and Q.Q.
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The authors declare no competing interests.
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Ethics approval of all the relevant GWAS was obtained from the respective institutional review boards. For instance, the FinnGen project was approved by the Coordinating Ethics Committee of the Helsinki and Uusimaa Hospital District. Therefore, additional ethics review was not required for this MR study using previously reported data.
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Liang, K., Qiao, Q., Yang, M. et al. Association of congenital iodine deficiency syndrome and differentiated thyroid cancer: a Mendelian randomization study. Pediatr Res 95, 1331–1334 (2024). https://doi.org/10.1038/s41390-023-02971-x
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DOI: https://doi.org/10.1038/s41390-023-02971-x