The Association between High Dose Radioactive Iodine Therapy and Telomeric and Chromosomal Damage in Thyroid Cancer Patients

Abstract

Radioactive iodine (RAI) therapy has been specialized to treatment of differentiated thyroid carcinoma during several decades, contributing the improvement of cancer survival. However, there were also concerns about internal radiation hazard from radioactive iodine, suggested by several epidemiologic studies that reported higher second malignancy rates in thyroid cancer patients with RAI treatment. Given these epidemiologic or experimental findings, cumulative doses for RAI treatment is recommended not to exceed over 600mCi

however, there were few studies about long term carcinogenic effects of RAI treatment. This study was designed to examine the changes of clinical outcomes and the incidence of second malignancies in thyroid cancer patients and to evaluate the association between high dose RAI therapy and telomeric and chromosomal damages. To examine telomeric damages in thyroid cancer patient with or without RAI treatment, relative telomere length (RTL) and hTERT mRNA expression were measured and compared among RAI cumulative doses. Chromosomal damage was estimated by chromosomal fragility test, used in diagnosis of Fanconi disease that is characterized by easy chromosomal breakages and malignancy risk. In this study, during 4 decades, recurrence rate of thyroid cancer was decreasing with more favorable changes in pathological characteristics and increasing rate of RAI treatment. Compared with general population, the incidence of second malignancy after thyroid cancer treatment was significantly higher especially in patients with extremely high dose of RAI over 1000mCi. Of 505 cases used in analyses of relative telomere length, RTL showed trends of being shorter in patients with high dose of RAI treatment and was observed to be a significant correlation in multivariate analyses. This inversed correlation between RTL and RAI dose was more prominently observed in patients with higher RAI dose over 300mCi. Expression of hTERT mRNA did not show significant association with RAI doses. Chromosomal fragility was observed in patients with RAI treatment

however, the subgroup analysis by age groups showed that, only in older age groups over 40 years, corresponding trend was observed without statistical significances. In this study, a parameter of telomere length and a parameter of chromosomal fragility showed significant differences between two groups lower and upper than 100mCi and higher doses of cumulative RAI dose. However, in other parameters, there were significant differences at any cut-off doses. In summary, patients with higher dose RAI therapy tended to have shorter RTL, especially in patients group younger than 60 years old, and hTERT mRNA expression and chromosomal fragility were not associated with cumulative RAI dose. Despite limitation in interpretation, the results suggested the cut-off dose showing statistical significances from 100mCi.