Avsar Fevzi Necati, Abbasoğlu Semra Doğru, Ademoğlu Evin, Sahutoglu Tuncay
Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, İstanbul, Türkiye.
Department of Medical Biochemistry, Istanbul Faculty of Medicine, Istanbul University, İstanbul, Türkiye.
Endocrine. 2025 May 26. doi: 10.1007/s12020-025-04288-7.
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.
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.
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.
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.
本研究旨在评估接受高剂量放射性碘（RAI，≥100mCi）治疗的分化型甲状腺癌（DTC）患者的氧化性DNA损伤及其与DNA修复酶多态性的关联。还探讨了DNA损伤标志物、基因变异与临床或肿瘤特征之间的关系。
纳入了来自土耳其人群的79例DTC患者以及59例年龄和性别匹配的对照。通过酶联免疫吸附测定法（ELISA）在RAI治疗前、治疗后2周和3个月时测量尿中8-羟基-2'-脱氧鸟苷（8-氧代鸟嘌呤，8-oxoG），这是一种氧化性DNA损伤的标志物。使用实时聚合酶链反应（PCR）和熔解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。
尿中8-氧代鸟嘌呤水平随时间呈非显著性上升趋势（p = 0.252）。患者中hOGG1的Cys/Cys基因型比对照组更常见（13%对6%，p = 0.54），而患者中Ser/Cys基因型明显较少见（36.7%对57.6%；比值比：0.46，95%置信区间：0.22 - 0.94，p = 0.03）。患者中Cys等位基因频率为0.32，对照组为0.35。两组之间APE1基因型和等位基因分布无显著差异。未发现多态性与8-氧代鸟嘌呤水平或临床特征之间存在关联，包括DTC亚型、肿瘤分期、性别、吸烟状况或年龄。
这是第一项在接受RAI治疗的土耳其DTC患者中联合评估尿中8-氧代鸟嘌呤和hOGG1/APE1多态性的研究。未发现与氧化性DNA损伤或临床特征存在一致的关联。需要更大规模的研究来验证这些发现。
