Oxidative DNA damage and DNA repair gene variants in differentiated thyroid cancer patients treated with radioactive iodine.

IF 3.7 3区 医学 Q2 Medicine
Fevzi Necati Avsar, Semra Doğru Abbasoğlu, Evin Ademoğlu, Tuncay Sahutoglu
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Abstract

Purpose: This study aimed to evaluate oxidative DNA damage and its association with polymorphisms in DNA repair enzymes among patients with differentiated thyroid cancer (DTC) treated with high-dose radioactive iodine (RAI, ≥100 mCi). Relationships between DNA damage markers, gene variants, and clinical or tumor characteristics were also explored.

Methods: Seventy-nine patients with DTC and 59 age and sex matched controls from a Turkish population were included. Urinary 8-hydroxy-2'-deoxyguanosine (8-oxoG), a marker of oxidative DNA damage, was measured by ELISA at baseline, 2 weeks, and 3 months post-RAI. Genotyping for hOGG1 Ser326Cys and APE1 Asp148Glu polymorphisms was performed on leukocyte-derived DNA using real-time PCR and melting curve analysis.

Results: Urinary 8-oxoG levels showed a non-significant upward trend over time (p = 0.252). The Cys/Cys genotype of hOGG1 was more frequent in patients than controls (13 vs. 6%, p = 0.54), while the Ser/Cys genotype was significantly less frequent in patients (36.7 vs. 57.6%; OR: 0.46, 95% CI: 0.22-0.94, p = 0.03). Cys allele frequencies were 0.32 in patients and 0.35 in controls. APE1 genotype and allele distributions did not differ significantly between groups. No associations were found between polymorphisms and 8-oxoG levels or clinical features, including DTC subtype, tumor stage, sex, smoking status, or age.

Conclusion: This is the first study to jointly evaluate urinary 8-oxoG and hOGG1/APE1 polymorphisms in Turkish DTC patients receiving RAI. No consistent associations were found with oxidative DNA damage or clinical characteristics. Larger studies are needed to validate these findings.

放射性碘治疗分化型甲状腺癌患者的DNA氧化损伤和DNA修复基因变异
目的:本研究旨在评估高剂量放射性碘(RAI,≥100 mCi)治疗分化型甲状腺癌(DTC)患者DNA氧化损伤及其与DNA修复酶多态性的关系。还探讨了DNA损伤标记物、基因变异与临床或肿瘤特征之间的关系。方法:纳入来自土耳其人群的79例DTC患者和59例年龄和性别匹配的对照组。尿8-羟基-2'-脱氧鸟苷(8-oxoG)是氧化DNA损伤的标志物,在rai后基线、2周和3个月用ELISA法测定。利用实时荧光定量PCR和熔融曲线分析对白细胞来源的DNA进行hOGG1 Ser326Cys和APE1 Asp148Glu多态性的基因分型。结果:尿8-oxoG水平随时间呈不显著上升趋势(p = 0.252)。hOGG1的Cys/Cys基因型在患者中比在对照组中更常见(13 vs. 6%, p = 0.54),而Ser/Cys基因型在患者中明显更少(36.7% vs. 57.6%;OR: 0.46, 95% CI: 0.22-0.94, p = 0.03)。患者的Cys等位基因频率为0.32,对照组为0.35。各组间APE1基因型和等位基因分布无显著差异。未发现多态性与8-oxoG水平或临床特征(包括DTC亚型、肿瘤分期、性别、吸烟状况或年龄)之间存在关联。结论:这是首个联合评估土耳其接受RAI的DTC患者尿8-oxoG和hOGG1/APE1多态性的研究。与DNA氧化损伤或临床特征没有一致的关联。需要更大规模的研究来验证这些发现。
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来源期刊
Endocrine
Endocrine 医学-内分泌学与代谢
CiteScore
6.40
自引率
5.40%
发文量
0
期刊介绍: Well-established as a major journal in today’s rapidly advancing experimental and clinical research areas, Endocrine publishes original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical research in all the different fields of endocrinology and metabolism. Articles will be accepted based on peer-reviews, priority, and editorial decision. Invited reviews, mini-reviews and viewpoints on relevant pathophysiological and clinical topics, as well as Editorials on articles appearing in the Journal, are published. Unsolicited Editorials will be evaluated by the editorial team. Outcomes of scientific meetings, as well as guidelines and position statements, may be submitted. The Journal also considers special feature articles in the field of endocrine genetics and epigenetics, as well as articles devoted to novel methods and techniques in endocrinology. Endocrine covers controversial, clinical endocrine issues. Meta-analyses on endocrine and metabolic topics are also accepted. Descriptions of single clinical cases and/or small patients studies are not published unless of exceptional interest. However, reports of novel imaging studies and endocrine side effects in single patients may be considered. Research letters and letters to the editor related or unrelated to recently published articles can be submitted. Endocrine covers leading topics in endocrinology such as neuroendocrinology, pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, Type 1 and Type 2 diabetes, hormones of male and female reproduction, adrenal diseases pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.
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