Radioactive ¹³¹I (RAI) therapy has potential effects for the treatment of Graves disease (GD). However, whether RAI therapy for GD increases cancer risk remains controversial in medicine and public health. We aimed to investigate whether the risk of cancer increases in patients with GD receiving RAI therapy compared with those who did not. Methods: We used the Korean National Health Insurance Service’s National Health Information Database from 2004 to 2020 and defined GD as prescribing antithyroid drugs, RAI, or thyroidectomy as a treatment for GD (International Classification of Diseases, 10th revision, E05 group). We investigated the hazard ratios (HRs) of overall and site-specific cancers associated with RAI in patients with GD. Subsequent cancer was defined as a primary malignancy treated at least 1 y after RAI therapy. Results: In total, 10,737 patients with GD who received RAI therapy (7,193 women, 67.0%; mean age, 43.7 ± 13.4 y) were matched to 53,003 patients with GD who had never received RAI treatment (35,471 women, 66.9%; mean age, 43.8 ± 13.2 y) in a 1:4–5 ratio by age, sex, and health checkup data. The median follow-up duration was 8.7 y (interquartile range, 5.2–12.1 y), and the median cumulative RAI dose was 555 MBq (interquartile range, 370–630 MBq) in the RAI therapy group. During 2004–2020, the overall subsequent cancer rates were 5.66 and 5.84 per 1,000 person-years in the RAI and non-RAI groups, respectively, with an unadjusted HR of 0.97 (95% CI, 0.88–1.06); this remained at 0.96 (95% CI, 0.83–1.10) after adjustment for multiple clinical confounding factors. For cancer subtypes, the risk of leukemia was significantly increased, with an HR of 2.39 (95% CI, 1.17–4.91). However, a loss of statistical significance was observed after adjusting for confounding factors, which may be attributed to the limited number of absolute events. Moreover, cancer-specific mortality was not different between the RAI and the non-RAI groups, with an adjusted HR of 0.99 (95% CI, 0.66–1.47). Conclusion: This study identified that the overall cancer risk in patients with GD who received RAI therapy compared with those who did not was not significant in Korea. Further long-term studies are needed to determine the risks and advantages of RAI therapy in patients with GD.

放射性¹³¹ I (RAI) 疗法对治疗格雷夫斯病 (GD) 有潜在作用。然而，RAI 治疗 GD 是否会增加癌症风险在医学和公共卫生领域仍存在争议。我们的目的是调查接受 RAI 治疗的 GD 患者与未接受 RAI 治疗的患者相比，患癌症的风险是否增加。方法：我们使用2004年至2020年韩国国民健康保险服务的国民健康信息数据库，将GD定义为开抗甲状腺药物、RAI或甲状腺切除术作为GD的治疗方法（国际疾病分类，第10版，E05组）。我们调查了 GD 患者中与 RAI 相关的整体癌症和特定部位癌症的风险比 (HR)。后续癌症定义为 RAI 治疗后至少 1 年治疗的原发性恶性肿瘤。结果：总共 10,737 名接受 RAI 治疗的 GD 患者（7,193 名女性，67.0%；平均年龄，43.7 ± 13.4 岁）与 53,003 名从未接受过 RAI 治疗的 GD 患者相匹配（35,471 名女性，66.9%；平均年龄） , 43.8 ± 13.2 y)，按年龄、性别和健康检查数据，比例为 1:4-5。 RAI治疗组的中位随访时间为8.7年（四分位距，5.2-12.1年），中位累积RAI剂量为555 MBq（四分位距，370-630 MBq）。 2004年至2020年期间，RAI组和非RAI组的总体后续癌症发生率分别为每1000人年5.66例和5.84例，未经调整的HR为0.97（95% CI，0.88-1.06）；调整多个临床混杂因素后，该值仍保持在 0.96（95% CI，0.83-1.10）。对于癌症亚型，患白血病的风险显着增加，HR 为 2.39（95% CI，1.17-4.91）。然而，在调整混杂因素后观察到统计显着性的丧失，这可能归因于绝对事件数量有限。此外，RAI 组和非 RAI 组之间的癌症特异性死亡率没有差异，调整后的 HR 为 0.99（95% CI，0.66-1.47）。结论：本研究发现，在韩国，接受 RAI 治疗的 GD 患者与未接受 RAI 治疗的患者相比，总体癌症风险并不显着。需要进一步的长期研究来确定 RAI 治疗对 GD 患者的风险和优势。