与甲状腺癌患者放射性碘治疗不良反应相关的遗传标记物。

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

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;38(3):255-265. doi: 10.1515/dmpt-2023-0007. eCollection 2023 Sep 1.

DOI:10.1515/dmpt-2023-0007

PMID:37708952

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

放射性碘治疗被认为适用于某些具有显著复发风险、甲状腺癌远处转移或疾病特异性死亡率预测因素的患者。本研究旨在探讨参与 DNA 损伤反应和自噬过程的基因产物的多态性与甲状腺癌患者放射性碘治疗不良反应之间的关系。

方法

本研究纳入了 181 例（男 37 例，女 144 例；中位年龄 56 [41；66.3] 岁）经组织学证实的甲状腺癌病史并接受甲状腺切除术的患者，进行放射性碘治疗。采用等位基因特异性实时 PCR 检测、、、、和多态性。

结果

不良反应的频率如下：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 个月后出现涎腺炎迹象 25.2%。携带 rs1864183 TT 基因型的患者胃肠道症状发生频率更高（与 CC+CT 相比），携带 rs10514231 CC 基因型的患者脑部症状更频繁（与 CT+TT 相比），携带 rs1800469 AA 基因型的患者也有类似情况（与 AG+GG 相比）。rs10514231 的 CC 基因型增加了放射性碘引起的疲劳发生率，而 rs11212570 的 GA 基因型则对疲劳有保护作用。rs1800469 与放射性碘治疗 6 个月后的涎腺炎迹象有关。