Genetic markers associated with resistance to radioiodine therapy in thyroid cancer patients: Prospective cohort study

Background. The indication for radiotherapy in oncological practice are metastases of differentiated thyroid cancer after thyroidectomy, the presence of distant metastases, or stage N1b, or negative dynamics of blood thyroglobulin levels after thyroidectomy for thyroid cancer. The mechanism of actio...

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Published in:	Sovremennaia onkologiia : zhurnal kafedry onkologii RMAPO dlia nepreryvnogo poslediplomnogo obrazovaniia Vol. 24; no. 3; pp. 345 - 350
Main Authors:	Denisenko, Natalia P., Shuev, Grigorij N., Mukhamadiev, Reis H., Perfilieva, Oksana M., Kazakov, Ruslan E., Kachanova, Anastasia A., Milyutina, Olga I., Konenkova, Olga V., Ryzhkin, Sergey A., Ivashchenko, Dmitriy V., Bure, Irina V., Kirienko, Sergey L., Zhmaeva, Elena M., Mirzaev, Karin B., Ametov, Alexander S., Poddubnaya, Irina V., Sychev, Dmitry A.
Format:	Journal Article
Language:	English
Published:	IP Habib O.N 25-11-2022
Subjects:	131i radiotherapy resistance snps
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Summary:	Background. The indication for radiotherapy in oncological practice are metastases of differentiated thyroid cancer after thyroidectomy, the presence of distant metastases, or stage N1b, or negative dynamics of blood thyroglobulin levels after thyroidectomy for thyroid cancer. The mechanism of action of radiotherapy is based on provoking double-stranded DNA breaks. It is important to study the role of polymorphisms of NFKB1, ATM, ATG16L2 and ATG10 genes, products of which are involved in the processes of DNA damage response pathway and autophagy, in the formation of resistance to radioiodine therapy of thyroid cancer patients. Aim. To examine the association between NFKB1, ATM, ATG16L2 and ATG10 polymorphisms and resistance to radioiodine therapy in thyroid cancer patients. Materials and methods. The study included 181 patients (37 men, 144 women; mean age 53.515.7 years) with histologically confirmed thyroid cancer and a history of thyroidectomy who received radioiodine therapy. Carriage of single-nucleotide polymorphisms (rs230493) NFKB1, (rs11212570) ATM, (rs10898880) ATG16L2 and (rs10514231, rs1864183, rs4703533) ATG10 was determined by real-time PCR using TaqMan kits. Results. Among 181 patients, resistance to radioiodine therapy was observed in 11 (6.1%) cases. No significant associations between the individual polymorphisms and resistance to radioiodine therapy were obtained, p0.05. Haplotype analysis showed that carriage of the C-C ATG10 rs10514231-rs1864183 haplotype was associated with an increased risk of developing resistance to radioiodine therapy, p=0.04. Conclusion. Further studies on large samples of radioiodine therapy-resistant patients using whole-genome sequencing methods are required to specify the role of genetic factors in the response to 131I therapy.
ISSN:	1815-1434 1815-1442
DOI:	10.26442/18151434.2022.3.201867