Abstract 7350: Association between radioactive iodine treatment for hyperthyroidism and incident cancer

Abstract Background: Radioactive iodine (RAI) has been one of the main treatments for hyperthyroidism since the 1940’s. However, its long-term safety, particularly regarding cancer risk, remains unclear and controversial. This study aimed to evaluate the association between RAI treatment for hyperthyroidism and overall cancer risk as well as risk of site-specific cancers. Methods: We conducted a retrospective cohort study using the University of Michigan Precision Health database, which integrates clinical and administrative data from multiple sources, including records from electronic health records, pharmacy, cancer registries, and death registries. Our analytic sample included Michigan Medicine primary care patients aged 18 and older newly diagnosed with hyperthyroidism between 2006 and 2019 with no previous cancer diagnosis. Information on types of treatment for hyperthyroidism (RAI, anti-thyroid medications or thyroidectomy) was abstracted from electronic health records. Participants were followed until cancer diagnosis, death, or end of study (December 2022). Data for key covariates including age, sex, race, comorbidities, BMI, smoking and alcohol history were extracted. Associations between hyperthyroidism treatment and risk of overall and site-specific cancers with at least 20 cases (Breast, Melanoma, Cervix, Prostate, Brain/CNS, Bladder and Colon) were estimated using Cox proportional hazards models. Treatment type was modeled as a time-dependent variable (RAI vs. other treatment) and the analysis included both age-adjusted (age adj) models and multivariable (mv) models which adjusted for age, sex, BMI, comorbidities and severity of hyperthyroidism. MV models for breast, cervix, and prostate cancer did not include sex as these models were restricted to women or men, as appropriate. Results: A total of 6435 participants were included in the analysis, contributing 52, 782 total person-years of follow-up. A total 487 cases of cancer were diagnosed. Compared to patients treated with either medication or thyroidectomy, RAI treatment was not significantly associated with an increased risk of overall cancer (age adj-HR = 0.93 [95% CI: 0.77-1.13], p=0.46; mv-HR= 1.02 [95% CI: 0.73-1.41], p=0.93). In site-specific cancer analyses, RAI treatment was associated with a significant increase in risk of breast cancer in the age adj-HR = 1.70 [95% CI: 1.16-2.40], p=0.04 and remained significant in the multivariable model HR = 2.24 [1.21-4.17], p=0.03). No significant associations were identified between RAI treatment and other site-specific cancers. Conclusions: In this cohort study, RAI treatment for hyperthyroidism was associated with a significantly increased risk of breast cancer but showed no consistent association with overall cancer risk. Citation Format: Harry D. Momo, Megan R. Haymart, Xu Shi, Alison M. Mondul. Association between radioactive iodine treatment for hyperthyroidism and incident cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7350.