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

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

  • Pharmacology (medical)
  • General Pharmacology, Toxicology and Pharmaceutics
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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.

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