The Association between High Dose Radioactive Iodine Therapy and Telomeric and Chromosomal Damage in Thyroid Cancer Patients
갑상선암 환자에서 고용량 방사성 요오드 치료와 텔로미어 및 염색체 손상 간의 연관성

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dc.description학위논문 (박사)-- 서울대학교 대학원 : 의과대학 의학과 분자유전체의학전공, 2016. 2. 박도준.-
dc.description.abstractRadioactive 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-
dc.description.abstracthowever, 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-
dc.description.abstracthowever, 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.-
dc.description.tableofcontents1.Introduction 1

2.Methods 4
2.1.Subjects 4
2.2.Treatment and follow-up strategy and definition of recurrence 5
2.3.Reverse transcriptase PCR of hTERT mRNA expressions 5
2.4.Measurement of Relative Telomere Length (RTL) 7
2.5.Chromosomal Fragility test 11
2.6.Statistics 11

3.Results 13
3.1.Secular trends of papillary thyroid cancer in Korea 13
3.2. Incidence of second primary malignancy and association with high dose RAI therapy 13
3.3.The association between RAI dose and relative telomere length 18
3.4.The association between RAI dose and hTERT mRNA expression 32
3.5.The association between RAI dose and chromosomal fragility 36
3.6.Correlations among three parameters representing telomeric and chromosomal damages 40
3.7.Cut-off levels of RAI cumulative doses associated with telomere shortening or chromosomal fragility 42

4. Discussion 49

Reference 53

국문초록 58
dc.format.extent3876449 bytes-
dc.publisher서울대학교 대학원-
dc.subjectradioactive iodine-
dc.subjectcumulative dose-
dc.subjectthyroid cancer-
dc.subjectsecond malignancy-
dc.subjectchromosomal fragility-
dc.titleThe Association between High Dose Radioactive Iodine Therapy and Telomeric and Chromosomal Damage in Thyroid Cancer Patients-
dc.title.alternative갑상선암 환자에서 고용량 방사성 요오드 치료와 텔로미어 및 염색체 손상 간의 연관성-
dc.citation.pagesvii, 59-
dc.contributor.affiliation의과대학 의학과-
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Theses (Ph.D. / Sc.D._의학과)
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