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Licensed Unlicensed Requires Authentication Published by De Gruyter June 30, 2023

Genetic markers associated with adverse reactions of radioiodine therapy in thyroid cancer patients

  • Natalia P. Denisenko ORCID logo EMAIL logo , Anastasia A. Kachanova ORCID logo , Ivan V. Sychev ORCID logo , Gregory N. Shuev ORCID logo , Oksana M. Perfilieva , Reis H. Mukhamadiev ORCID logo , Ruslan E. Kazakov ORCID logo , Olga I. Milyutina ORCID logo , Olga V. Konenkova ORCID logo , Sergey A. Ryzhkin ORCID logo , Elena M. Zhmaeva , Sergey L. Kirienko , Dmitriy V. Ivashchenko ORCID logo , Irina V. Bure ORCID logo , Alexander S. Ametov , Irina V. Poddubnaya ORCID logo , Karin B. Mirzaev ORCID logo and Dmitry A. Sychev ORCID logo

Abstract

Objectives

Radioactive iodine therapy is considered for patients with certain clinicopathological factors that predict a significant risk of recurrence, distant metastases of thyroid cancer or disease-specific mortality. The aim of the study was to investigate the association between polymorphisms of genes, products of which are involved in the processes of DNA damage response and autophagy, and the adverse reactions of radioiodine therapy in thyroid cancer patients.

Methods

The study included 181 patients (37 men, 144 women; median age 56 [41; 66.3] years) with histologically confirmed thyroid cancer and a history of thyroidectomy who received radioiodine therapy. NFKB1, ATM, ATG16L2, ATG10, TGFB1, and TNF polymorphisms were determined by allele-specific realtime-PCR.

Results

The frequency of adverse reactions was the following: gastrointestinal symptoms – 57.9 %, local symptoms – 65.8 %, cerebral symptoms – 46.8 %, fatigue – 54.4 %; signs of sialoadenitis six months after radioiodine therapy – 25.2 %. TT genotype carriers of ATG10 rs1864183 had higher frequency of gastrointestinal symptoms (vs. CC+CT), the CC genotype carriers of ATG10 rs10514231 had significantly more frequent cerebral symptoms (vs. CT+TT), as well as AA genotype carriers of TGFB1 rs1800469 (vs. AG+GG). CC genotype of ATG10 rs10514231 increased the incidence of radioiodine-induced fatigue, whereas GA genotype of the ATM rs11212570 had a protective role against fatigue. TGFB1 rs1800469 was associated with signs of sialoadenitis six months after radioiodine therapy.

Conclusions

Genetic factors may contribute to the occurrence of adverse reactions of radioiodine therapy in thyroid cancer patients.


Corresponding author: Natalia P. Denisenko, Cand. Sci. (Med.), Research Laboratory of Neuroendocrine Tumors, Centre for Personalized Medicine, Saint-Petersburg, Russia; and Research Institute of Molecular and Personalized Medicine, Russian Medical Academy of Continuous Professional Education, Moscow, Russia, Phone: +7 (495) 945 81 39, Fax: +7 (499) 254-98-05, E-mail:

  1. Research funding: This work was financially supported by the Ministry of Science and Higher Education of the Russian Federation (Agreement No. 075-15-2022-301).

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: Research involving human subjects complied with all relevant national regulations, institutional policies and is in accordance with the tenets of the Helsinki Declaration (as revised in 2013), and has been approved by the local ethics committee of Russian Medical Academy of Continuous Professional Education (9th February, 2021).

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/dmpt-2023-0007).


Received: 2023-02-07
Accepted: 2023-05-08
Published Online: 2023-06-30

© 2023 Walter de Gruyter GmbH, Berlin/Boston

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