甲状腺癌患者中与放射性碘治疗不良反应相关的基因标志物。

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

作者信息

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

机构信息

Research Laboratory of Neuroendocrine Tumors, Centre for Personalized Medicine, Saint-Petersburg, Russia.

Research Institute of Molecular and Personalized Medicine, Russian Medical Academy of Continuous Professional Education, Moscow, Russia.

出版信息

Drug Metab Pers Ther. 2023 Jun 30. doi: 10.1515/dmdi-2023-0007.

DOI:10.1515/dmdi-2023-0007

PMID:37381702

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. , , , , , and 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 rs1864183 had higher frequency of gastrointestinal symptoms (vs. CC+CT), the CC genotype carriers of rs10514231 had significantly more frequent cerebral symptoms (vs. CT+TT), as well as AA genotype carriers of rs1800469 (vs. AG+GG). CC genotype of rs10514231 increased the incidence of radioiodine-induced fatigue, whereas GA genotype of the rs11212570 had a protective role against fatigue. 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.

摘要

目的

对于具有某些临床病理因素、预示复发风险高、甲状腺癌远处转移或疾病特异性死亡风险高的患者，会考虑采用放射性碘治疗。本研究的目的是调查基因多态性与甲状腺癌患者放射性碘治疗不良反应之间的关联，这些基因的产物参与DNA损伤反应和自噬过程。

方法

本研究纳入了181例组织学确诊为甲状腺癌且有甲状腺切除术史并接受放射性碘治疗的患者（37例男性，144例女性；中位年龄56[41；66.3]岁）。通过等位基因特异性实时PCR测定了……、……、……、……、……和……多态性。

结果

不良反应的发生率如下：胃肠道症状-57.9%，局部症状-65.8%，脑部症状-46.8%，疲劳-54.4%；放射性碘治疗6个月后涎腺炎体征-25.2%。rs1864183的TT基因型携带者胃肠道症状发生率较高（与CC+CT相比），rs10514231的CC基因型携带者脑部症状明显更频繁（与CT+TT相比），以及rs1800469的AA基因型携带者（与AG+GG相比）。rs10514231的CC基因型增加了放射性碘诱导的疲劳发生率，而rs11212570的GA基因型对疲劳有保护作用。rs1800469与放射性碘治疗6个月后的涎腺炎体征有关。