Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Clinical Research Article
  • Published:

Association of congenital iodine deficiency syndrome and differentiated thyroid cancer: a Mendelian randomization study

Pediatric Research volume 95, pages 1331–1334 (2024)Cite this article

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: The experimental design of our study and the there assumptions of the MR analysis.
Fig. 2: Flow chart of screening SNPs as instrumental variables in our study.
Fig. 3: Mendelian randomization analysis evaluating the causal effects of host genetic liability to congenital iodine deficiency syndrome on differentiated thyroid cancer.

Similar content being viewed by others

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.

References

  1. Filetti, S. et al. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann. Oncol. : Off. J. Eur. Soc. Med. Oncol. 30, 1856–1883 (2019).

    Article  CAS  Google Scholar 

  2. Reiners, C. & Drozd, V. Editorial: radiation as risk factor, early diagnosis, therapy, and follow-up of differentiated thyroid cancer. Front. Endocrinol. 12, 797969 (2021).

    Article  Google Scholar 

  3. Barrea, L. et al. Nutritional status and follicular-derived thyroid cancer: an update. Crit. Rev. Food Sci. Nutr. 61, 25–59 (2021).

    Article  CAS  PubMed  Google Scholar 

  4. Zimmermann, M. B. & Boelaert, K. Iodine deficiency and thyroid disorders. Lancet Diabetes Endocrinol. 3, 286–295 (2015).

    Article  CAS  PubMed  Google Scholar 

  5. Skrivankova, V. W. et al. Strengthening the reporting of observational studies in epidemiology using Mendelian randomization: the STROBE-MR statement. JAMA 326, 1614–1621 (2021).

    Article  PubMed  Google Scholar 

  6. Gala, H. & Tomlinson, I. The use of Mendelian randomization to identify causal cancer risk factors: promise and limitations. J. Pathol. 250, 541–554 (2020).

    Article  PubMed  Google Scholar 

  7. Sekula, P., Del Greco, M. F., Pattaro, C. & Köttgen, A. Mendelian randomization as an approach to assess causality using observational data. J. Am. Soc. Nephrol. 27, 3253–3265 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Kurki, M.I. et al. FinnGen provides genetic insights from a well-phenotyped isolated population. Nature. 613, 508–518 (2023).

  9. Reische, E. C. et al. The joint role of iodine status and thyroid function on risk for preeclampsia in finnish women: a population-based nested case-control study. Biol. Trace Elem. Res. 199, 2131–2137 (2021).

    Article  CAS  PubMed  Google Scholar 

  10. Ley, D. & Turck, D. Iodine supplementation: is there a need? Curr. Opin. Clin. Nutr. Metab. Care 24, 265–270 (2021).

    Article  PubMed  Google Scholar 

  11. Köhler, A. et al. Genome-wide association study on differentiated thyroid cancer. J. Clin. Endocrinol. Metab. 98, E1674–E1681 (2013).

    Article  PubMed  Google Scholar 

  12. Larsson, S. C., Burgess, S., Mason, A. M. & Michaëlsson, K. Alcohol consumption and cardiovascular disease: a Mendelian randomization study. Circ. Genom. Precis. Med. 13, e002814 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wu, F., Huang, Y., Hu, J. & Shao, Z. Mendelian randomization study of inflammatory bowel disease and bone mineral density. BMC Med. 18, 312 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Chen, X. et al. Causal relationship between physical activity, leisure sedentary behaviors and COVID-19 risk: a Mendelian randomization study. J. Transl. Med. 20, 216 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Papadimitriou, N. et al. Physical activity and risks of breast and colorectal cancer: a Mendelian randomisation analysis. Nat. Commun. 11, 597 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cléro, É. et al. Dietary iodine and thyroid cancer risk in French Polynesia: a case-control study. Thyroid. 22, 422–429 (2012).

    Article  PubMed  Google Scholar 

  17. Ren, Y. et al. FOXE1 polymorphism interacts with dietary iodine intake in differentiated thyroid cancer risk in the Cuban population. Thyroid. 26, 1752–1760 (2016).

    Article  CAS  PubMed  Google Scholar 

  18. Axelrad, A. A. & Leblond, C. P. Induction of thyroid tumors in rats by a low iodine diet. Cancer 8, 339–367 (1955).

    Article  CAS  PubMed  Google Scholar 

  19. al-Saadi, A. A. & Beierwaltes, W. H. Chromosomal changes in rat thyroid cells during iodine depletion and repletion. Cancer Res. 26, 676–688 (1966).

    CAS  PubMed  Google Scholar 

  20. Lazarus, J. H. Iodine status in Europe in 2014. Eur. Thyroid J. 3, 3–6 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Ittermann, T. et al. Standardized map of iodine status in Europe. Thyroid. 30, 1346–1354 (2020).

    Article  CAS  PubMed  Google Scholar 

  22. Brion, M. J., Shakhbazov, K. & Visscher, P. M. Calculating statistical power in Mendelian randomization studies. Int J. Epidemiol. 42, 1497–1501 (2013).

    Article  PubMed  Google Scholar 

Download references

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.

Author information

Author notes

  1. These authors contributed equally: Kai Liang, Qincheng Qiao.

Authors and Affiliations

  1. Department of Endocrine and Metabolic Diseases, Qilu Hospital of Shandong University, Jinan, China

    Kai Liang, Qincheng Qiao, Mengmeng Yang, Yan Liu, Peng Lin, Li Chen & Xinguo Hou

  2. Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, China

    Kai Liang, Peng Lin, Li Chen & Xinguo Hou

  3. Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province medicine & health, Jinan, China

    Kai Liang, Peng Lin, Li Chen & Xinguo Hou

  4. Jinan Clinical Research Center for Endocrine and Metabolic Diseases, Jinan, China

    Kai Liang, Peng Lin, Li Chen & Xinguo Hou

  5. The First Clinical Medical College, Cheeloo College of Medicine, Shandong University, Jinan, China

    Qincheng Qiao & Mengmeng Yang

Authors
  1. Kai Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qincheng Qiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mengmeng Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Peng Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Li Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xinguo Hou
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

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.

Corresponding authors

Correspondence to Li Chen or Xinguo Hou.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval

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.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41390-023-02971-x

Search

Advanced search

Quick links