臺灣博碩士論文加值系統

高劑量游離輻射的致癌性已被證實，但低劑量率游離輻射的致癌性目前尚未有一致的定論，對於長期低劑量率游離輻射暴露，所可能產生的健康危害應該更被重視。臺灣於1992年8月爆發第一起輻射污染鋼筋屋事件，截至目前，約有10,000人曾遭受長期低劑量率游離輻射的暴露，長期追蹤此族群的癌症發生風險，將有助於釐清長期低劑量率游離輻射的致癌風險。

截至2002年12月底，本研究登錄的暴露族群總人數為7,271人，與全國癌症發生登記檔進行資料比對，結果顯示，暴露族群罹癌總數為141人，其中有46人，自輻射暴露開始至罹癌的時間，小於ICRP60號所建議之最短潛伏期。本研究為評估長期低劑量率游離輻射暴露人群罹癌的風險，矯正潛伏期、年齡與性別後，計算年齡標準化發生率，並與國內未暴露族群進行比較，同時以Poisson regression model評估劑量效應關係，並以Cox regression model估計增加危險比。

結果顯示：男性罹患血癌(排除慢性淋巴性血癌)(n = 6, SIR = 3.6, 95% confidence interval [CI] 1.2 – 7.4)之風險有統計上顯著增高；女性罹患甲狀腺癌(n = 6, SIR = 2.6, 95% CI 1.0 – 5.7)之風險有統計上邊緣顯著增高。劑量效應評估顯示：第一次暴露年齡低於(含)30歲者，罹患癌症特別是實質癌，有統計上顯著的劑量效應關係。每增加100毫西弗 (100 mSv)輻射暴露劑量之相對危險比，結果顯示，暴露族群罹患血癌(排除慢性淋巴性血癌) (excess hazard ratio; EHR100 mSv = 1.19, 95% CI 1.02 – 1.38)之增加危險比有統計上顯著增高；肺癌 (EHR100 mSv = 1.12, 95% CI 1.0 – 1.27)、乳癌 (EHR100 mSv = 1.12, 95% CI 1.0 – 1.25)之增加危險比有統計上邊緣顯著增高。

本研究結果顯示，長期低劑量率游離輻射暴露，會提高暴露者發生癌症的風險，尤其是血癌(排除慢性淋巴性血癌)。由於輻射誘發實質癌的潛伏期較長，而台灣輻射污染建築物暴露族群，截至2002年止，平均追蹤時間為16 年，因此，持續追蹤此族群的罹癌風險，將能提供更多的證據以加強本研究結果的準確性。

The carcinogenicity of exposure to high dose ionizing radiation has been well documented. A consensus has not been reached on the carcinogenic effect of chronic low dose radiation exposure. It well more concern for the health effect induced by prolonged low dose rate radiation exposure. An accident of 60Co-contaminated building was broken out on August 1992 in Taiwan. Until now, there were around 10,000 individuals that they had exposed to prolong low dose-rate radiation exposure. Follow-up the cancer risks of this exposed population well helpful to clarify the carcinogenic effect of chronic low dose radiation exposure.

Until December, 2002 there were 7,271 people registered as the study cohort. In addition, by matching cohort members’ National Identification Numbers (NIN) with the NIN of the cases registered by the National Cancer Registry of Taiwan (NCRT), we were able to identify cancer patients amongst the study cohort. A total of 141 cohort members were found to have developed cancers, and 46 of these cases developed in less than the minimal latent periods, as recommended by the ICRP 60. The cancer risks were compared with those populations with the same temporal and geographic characteristics in Taiwan by standardized incidence ratios (SIRs), adjustment for age, gender, and latent periods since the initial exposure. These risks were further associated with cumulative radiation exposure via Poisson regression analyses. Excess hazard ratios (EHRs) with 100 millisievert (mSv) exposure (EHR100 mSv) were assessed using the Cox proportional hazard models.

The risks were significantly increased for all leukemia combined except for chronic lymphocytic leukemia (n = 6, SIR = 3.6, 95% confidence interval [CI] 1.2, 7.4) in men. The risk of thyroid cancers (n = 6, SIR = 2.6, 95% CI 1.0, 5.7) was marginally significant elevated in women. All cancers combined and all solid cancers combined also showed exposure-dependent increased risks in individuals with the initial exposure at ages less than 30 years old, but not beyond this age. Significant higher EHR100 mSv were observed in leukemia (excluding chronic lymphocytic leukemia; EHR100 mSv 1.19, 95% CI 1.02, 1.38), while marginally significant higher EHR100 mSv were shown in lung cancers (EHR100 mSv 1.12, 95% CI 1.0, 1.27), and breast cancers (EHR100 mSv 1.12, 95% CI 1.0, 1.25).

The results suggest that prolonged low dose-rate radiation exposure appeared to increase risks of developing certain cancers, especially for leukemia (excluding chronic lymphocytic leukemia). The average follow-up period since initial exposure was still too short (mean 16 years) to observe the development of the whole spectrum of cancers in this cohort. Further follow-up of the study cohort is necessary to corroborate our findings and identify other types of cancers that may also be related to the protracted and low dose-rate ionizing radiation.

誌謝..............................................................................................................I
中文摘要....................................................................................................II
英文摘要...................................................................................................IV
目錄……………………………………………………………………...VI
表目錄....................................................................................................VIII圖目錄…………………………………………………………………...X
第一章 緒論 1
第一節 研究背景與動機 1
第二章 文獻探討 3
2-1 游離輻射產生健康效應的過程 3
2-2 游離輻射與癌症風險研究 4
第三章 材料與方法 12
3-1研究族群 12
3-2 癌症個案的診斷 12
3-3 對照族群 13
3-4 人年的計算 13
3-5 物理劑量推估 14
第四章 標準化發生率及相對風險估計 18
4-1 材料與方法 18
4-2 結果 21
4-3 討論 27
第五章 增加危險比估計 30
5-1 材料與方法 30
5-2 結果 31
5-3 討論 32
第六章 討論 35
6-1 癌症風險評估指標之比較 36
6-2篩檢效應 39
6-3物理劑量推估的準確性 39
6-4 研究限制 40
第七章 結論與建議 41
第八章 參考文獻 43

1. Chang WP, Chan CC, Wang JD. 60Co contamination in recycled steel resulting in elevated civilian radiation doses: causes and challenges. Health Phys. 1997;73(3):465-72.
2. Chang WP CC. Radioactive contamination in Taiwan: An update. Health physics Newsletter 1998;26:22.
3. 梁佑任. 低劑量游離輻射之癌症風險評估. 低劑量游離輻射之癌症風險評估. 國立成功大學 碩士論文 2000.
4. ICRP. Recommendations on the International Commission on Radiological Protection. Publication 60. . Ann ICRP: New York 1990.
5. Brenner DJ, Doll R, Goodhead DT, et al. Cancer risks attributable to low doses of ionizing radiation: assessing what we really know. Proc Natl Acad Sci U S A 2003;100(24):13761-6.
6. Wall BF, Kendall GM, Edwards AA, Bouffler S, Muirhead CR, Meara JR. What are the risks from medical X-rays and other low dose radiation? Br J Radiol 2006;79(940):285-94.
7. Thompson DE, Mabuchi K, Ron E, et al. Cancer incidence in atomic bomb survivors. Part II: Solid tumors, 1958-1987. Radiat Res 1994;137(2 Suppl):S17-67.
8. Preston DL, Kusumi S, Tomonaga M, et al. Cancer incidence in atomic bomb survivors. Part III. Leukemia, lymphoma and multiple myeloma, 1950-1987. Radiat Res 1994;137(2 Suppl):S68-97.
9. Land CE, Tokunaga M, Koyama K, et al. Incidence of female breast cancer among atomic bomb survivors, Hiroshima and Nagasaki, 1950-1990. Radiat Res 2003;160(6):707-17.
10. Cologne JB, Tokuoka S, Beebe GW, Fukuhara T, Mabuchi K. Effects of radiation on incidence of primary liver cancer among atomic bomb survivors. Radiat Res 1999;152(4):364-73.
11. Pierce DA, Shimizu Y, Preston DL, Vaeth M, Mabuchi K. Studies of the mortality of atomic bomb survivors. Report 12, Part I. Cancer: 1950-1990. Radiat Res 1996;146(1):1-27.
12. Preston DL, Shimizu Y, Pierce DA, Suyama A, Mabuchi K. Studies of mortality of atomic bomb survivors. Report 13: Solid cancer and noncancer disease mortality: 1950-1997. Radiat Res 2003;160(4):381-407.
13. Ivanov VK, Tsyb AF, Gorsky AI, et al. Leukaemia and thyroid cancer in emergency workers of the Chernobyl accident: estimation of radiation risks (1986-1995). Radiat Environ Biophys 1997;36(1):9-16.
14. Noshchenko AG, Moysich KB, Bondar A, Zamostyan PV, Drosdova VD, Michalek AM. Patterns of acute leukaemia occurrence among children in the Chernobyl region. Int J Epidemiol 2001;30(1):125-9.
15. Hatch M, Ron E, Bouville A, Zablotska L, Howe G. The Chernobyl disaster: cancer following the accident at the Chernobyl nuclear power plant. Epidemiol Rev 2005;27:56-66.
16. Ivanov VK, Tsyb AF, Petrov AV, Maksioutov MA, Shilyaeva TP, Kochergina EV. Thyroid cancer incidence among liquidators of the Chernobyl accident. Absence of dependence of radiation risks on external radiation dose. Radiat Environ Biophys 2002;41(3):195-8.
17. Prisyazhiuk A, Pjatak OA, Buzanov VA, Reeves GK, Beral V. Cancer in the Ukraine, post-Chernobyl. Lancet 1991;338(8778):1334-5.
18. Kazakov VS, Demidchik EP, Astakhova LN. Thyroid cancer after Chernobyl. Nature 1992;359(6390):21.
19. Likhtarev IA, Sobolev BG, Kairo IA, et al. Thyroid cancer in the Ukraine. Nature 1995;375(6530):365.
20. Baverstock K, Egloff B, Pinchera A, Ruchti C, Williams D. Thyroid cancer after Chernobyl. Nature 1992;359(6390):21-2.
21. Abelin T, Egger M, Ruchti C. Fallout from Chernobyl. Belarus increase was probably caused by Chernobyl. Bmj 1994;309(6964):1298; author reply 1300.
22. Stsjazhko VA, Tsyb AF, Tronko ND, Souchkevitch G, Baverstock KF. Childhood thyroid cancer since accident at Chernobyl. Bmj 1995;310(6982):801.
23. Shilnikova NS, Preston DL, Ron E, et al. Cancer mortality risk among workers at the Mayak nuclear complex. Radiat Res 2003;159(6):787-98.
24. Gilbert ES, Koshurnikova NA, Sokolnikov ME, et al. Lung cancer in Mayak workers. Radiat Res 2004;162(5):505-16.
25. Kossenko MM, Degteva MO, Vyushkova OV, Preston DL, Mabuchi K, Kozheurov VP. Issues in the comparison of risk estimates for the population in the Techa River region and atomic bomb survivors. Radiat Res 1997;148(1):54-63.
26. Cardis E, Gilbert ES, Carpenter L, et al. Effects of low doses and low dose rates of external ionizing radiation: cancer mortality among nuclear industry workers in three countries. Radiat Res 1995;142(2):117-32.
27. Ritz B, Morgenstern H, Crawford-Brown D, Young B. The effects of internal radiation exposure on cancer mortality in nuclear workers at Rocketdyne/Atomics International. Environ Health Perspect 2000;108(8):743-51.
28. Sont WN, Zielinski JM, Ashmore JP, et al. First analysis of cancer incidence and occupational radiation exposure based on the National Dose Registry of Canada. Am J Epidemiol 2001;153(4):309-18.
29. Zablotska LB, Ashmore JP, Howe GR. Analysis of mortality among Canadian nuclear power industry workers after chronic low-dose exposure to ionizing radiation. Radiat Res 2004;161(6):633-41.
30. Auvinen A, Pukkala E, Hyvonen H, Hakama M, Rytomaa T. Cancer incidence among Finnish nuclear reactor workers. J Occup Environ Med 2002;44(7):634-8.
31. Gundestrup M, Storm HH. Radiation-induced acute myeloid leukaemia and other cancers in commercial jet cockpit crew: a population-based cohort study. Lancet 1999;354(9195):2029-31.
32. Stern FB, Waxweiler RA, Beaumont JJ, et al. A case-control study of leukemia at a naval nuclear shipyard. Am J Epidemiol 1986;123(6):980-92.
33. Beral V, Inskip H, Fraser P, Booth M, Coleman D, Rose G. Mortality of employees of the United Kingdom Atomic Energy Authority, 1946-1979. Br Med J (Clin Res Ed) 1985;291(6493):440-7.
34. Morin Doody M, Lonstein JE, Stovall M, Hacker DG, Luckyanov N, Land CE. Breast cancer mortality after diagnostic radiography: findings from the U.S. Scoliosis Cohort Study. Spine 2000;25(16):2052-63.
35. Ron E, Modan B, Preston D, Alfandary E, Stovall M, Boice JD, Jr. Thyroid neoplasia following low-dose radiation in childhood. Radiat Res 1989;120(3):516-31.
36. Weiss HA, Darby SC, Doll R. Cancer mortality following X-ray treatment for ankylosing spondylitis. Int J Cancer 1994;59(3):327-38.
37. Nyberg U, Nilsson B, Travis LB, Holm LE, Hall P. Cancer incidence among Swedish patients exposed to radioactive thorotrast: a forty-year follow-up survey. Radiat Res 2002;157(4):419-25.
38. Tao Z, Zha Y, Akiba S, et al. Cancer mortality in the high background radiation areas of Yangjiang, China during the period between 1979 and 1995. J Radiat Res (Tokyo) 2000;41 Suppl:31-41.
39. Sun Q, Akiba S, Tao Z, et al. Excess relative risk of solid cancer mortality after prolonged exposure to naturally occurring high background radiation in Yangjiang, China. J Radiat Res (Tokyo) 2000;41 Suppl:43-52.
40. Chang WP, Hwang BF, Wang D, Wang JD. Cytogenetic effect of chronic low-dose, low-dose-rate gamma-radiation in residents of irradiated buildings. Lancet 1997;350(9074):330-3.
41. Chang WP, Hsieh WA, Chen DP, et al. Change in centromeric and acentromeric micronucleus frequencies in human populations after chronic radiation exposure. Mutagenesis 1999;14(4):427-32.
42. Hsieh WA, Ni C, Hwang JJ, et al. Evaluation of the frequencies of chromosomal aberrations in a population exposed to prolonged low dose-rate 60Co gamma-irradiation. Int J Radiat Biol 2002;78(7):625-33.
43. Chang WP, Hwang JS, Hung MC, Hu TH, Lee SD, Hwang BF. Chronic low-dose gamma-radiation exposure and the alteration of the distribution of lymphocyte subpopulations in residents of radioactive buildings. Int J Radiat Biol 1999;75(10):1231-9.
44. Chen WL, Hwang JS, Hu TH, Chen MS, Chang WP. Lenticular opacities in populations exposed to chronic low-dose-rate gamma radiation from radiocontaminated buildings in Taiwan. Radiat Res 2001;156(1):71-7.
45. Wang JC, Lin YP, Hwang JS, Hsieh WH, Tsai YJ, Chang WP. Physical heights of children with prolonged low dose-rate gamma-radiation exposure in radiocontaminated buildings. Int J Radiat Biol 2001;77(1):117-25.
46. Chang TC, Chen WL, Chang WP, Chen CJ. Effect of prolonged radiation exposure on the thyroid gland of residents living in 60Co-contaminated rebar buildings. Int J Radiat Biol 2001;77(11):1117-22.
47. Wang JC LY, Hwang SL, Hsieh WA, Chen JC, Tang JL, Hwang JS, Lu WJ, Chang WP. Late haematological changes in population with chronic low dose-rate radiation exposure during childhood. British Journal of Radiology 2002;75:135-140.
48. NCRP. Mangement of Persons Accidentally Contanimnated with radionuclides. NCRP report No.65: Washington, DC 1980.
49. UNSCEAR. Sources, Effects and Risks of Ionizing Rradition UNSCEAR report: New York 1988.
50. NRPB. Risk of Radiation-induced Cancer at Low Dose and Low Dose Rates for Radiation Protection Purposes. Doc of NRPB 1995;6(1).
51. NCRP. Evaluation of the Linear Nonthreshold Dose-Response Model for Ionizing Radiation. NCRP report No.136: Washington, DC 2001.
52. UNSCEAR. Sources and effects of ionising radiation. Effects: Annex G. Biological effects at low radiation doses: New York 2000; 2.
53. Health Do. Cancer Registry. Department of Health, Executive Yuan.
54. 台灣輻射安全促進會. 1995.
55. WH O. International Classificarion of Diseases for Oncology (ICD-O). WHO, Geneva 1976.
56. 內政部統計處. 中華民國台閩地區人口統計-民國七十二年. 台北：內政部.
57. 內政部統計處. 中華民國台閩地區人口統計-民國七十三年. 台北：內政部.
58. 內政部統計處. 中華民國台閩地區人口統計-民國七十四年. 台北：內政部.
59. 內政部統計處. 中華民國台閩地區人口統計-民國七十五年. 台北：內政部.
60. 內政部統計處. 中華民國台閩地區人口統計-民國七十六年. 台北：內政部.
61. 內政部統計處. 中華民國台閩地區人口統計-民國七十七年. 台北：內政部.
62. 內政部統計處. 中華民國台閩地區人口統計-民國七十八年. 台北：內政部.
63. 內政部統計處. 中華民國台閩地區人口統計-民國七十九年. 台北：內政部.
64. 內政部統計處. 中華民國台閩地區人口統計-民國八十年. 台北：內政部.
65. 內政部統計處. 中華民國台閩地區人口統計-民國八十一年. 台北：內政部.
66. 內政部統計處. 中華民國台閩地區人口統計-民國八十二年. 台北：內政部.
67. 內政部統計處. 中華民國台閩地區人口統計-民國八十三年. 台北：內政部.
68. 內政部統計處. 中華民國台閩地區人口統計-民國八十四年. 台北：內政部.
69. 內政部統計處. 中華民國台閩地區人口統計-民國八十五年. 台北：內政部.
70. 內政部統計處. 中華民國台閩地區人口統計-民國八十六年. 台北：內政部.
71. 內政部統計處. 中華民國台閩地區人口統計-民國八十七年. 台北：內政部.
72. 內政部統計處. 中華民國台閩地區人口統計-民國八十八年. 台北：內政部.
73. 內政部統計處. 中華民國台閩地區人口統計-民國八十九年. 台北：內政部.
74. 內政部統計處. 中華民國台閩地區人口統計-民國九十年. 台北：內政部.
75. 內政部統計處. 中華民國台閩地區人口統計-民國九十一年. 台北：內政部.
76. BEIR. Health Effects of Exposure to Low Levels of Ionizing Radiation: BEIR V. The national Academy of Sciences: Washington, D.C. 1990.
77. Cardarelli J, 2nd, Elliott L, Hornung R, Chang WP. Proposed model for estimating dose to inhabitants of 60Co contaminated buildings. Health Phys 1997;72(3):351-60.
78. Hwang JS, Chan CC, Wang JD, Chang WP. Radiation exposure modeling for apartment living spaces with multiple radioactive sources. Health Phys 1998;74(3):379-86.
79. Breslow NE, Day, N.E. Statistical Methods in Cancer Research. The Design and Analysis of Cohort Studies 1987;Volume Ⅱ, Lyon: IARC.
80. Pearson ES H, HO. Biometrika tables for statisticians. London : Biometrika Trust 1976.
81. Folley JH, Borges W, Yamawaki T. Incidence of leukemia in survivors of the atomic bomb in Hiroshima and Nagasaki, Japan. Am J Med 1952;13(3):311-21.
82. Boice JD, Jr., Day NE, Andersen A, et al. Second cancers following radiation treatment for cervical cancer. An international collaboration among cancer registries. J Natl Cancer Inst 1985;74(5):955-75.
83. Weiss HA, Darby SC, Fearn T, Doll R. Leukemia mortality after X-ray treatment for ankylosing spondylitis. Radiat Res 1995;142(1):1-11.
84. Harvey EB, Boice JD, Jr., Honeyman M, Flannery JT. Prenatal x-ray exposure and childhood cancer in twins. N Engl J Med 1985;312(9):541-5.
85. Jacob P, Kenigsberg Y, Zvonova I, et al. Childhood exposure due to the Chernobyl accident and thyroid cancer risk in contaminated areas of Belarus and Russia. Br J Cancer 1999;80(9):1461-9.
86. Lowry R, Kann L, Collins JL, Kolbe LJ. The effect of socioeconomic status on chronic disease risk behaviors among US adolescents. Jama 1996;276(10):792-7.
87. Lantz PM, House JS, Lepkowski JM, Williams DR, Mero RP, Chen J. Socioeconomic factors, health behaviors, and mortality: results from a nationally representative prospective study of US adults. Jama 1998;279(21):1703-8.
88. Wardle J, Steptoe A. Socioeconomic differences in attitudes and beliefs about healthy lifestyles. J Epidemiol Community Health 2003;57(6):440-3.
89. Dickman PW, Sloggett A, Hills M, Hakulinen T. Regression models for relative survival. Stat Med 2004;23(1):51-64.
90. Pashayan N, Lepage C, Rachet B, Woods LM, Coleman MP. Survival trends for small intestinal cancer in England and Wales, 1971-1990: national population-based study. Br J Cancer 2006;95(9):1296-300.
91. Cardis E, Vrijheid M, Blettner M, et al. Risk of cancer after low doses of ionising radiation: retrospective cohort study in 15 countries. Bmj 2005;331(7508):77.
92. Ivanov VK, Rastopchin EM, Gorsky AI, Ryvkin VB. Cancer incidence among liquidators of the Chernobyl accident: solid tumors, 1986-1995. Health Phys 1998;74(3):309-15.
93. Boice JD, Jr., Preston D, Davis FG, Monson RR. Frequent chest X-ray fluoroscopy and breast cancer incidence among tuberculosis patients in Massachusetts. Radiat Res 1991;125(2):214-22.
94. Howe GR, McLaughlin J. Breast cancer mortality between 1950 and 1987 after exposure to fractionated moderate-dose-rate ionizing radiation in the Canadian fluoroscopy cohort study and a comparison with breast cancer mortality in the atomic bomb survivors study. Radiat Res 1996;145(6):694-707.
95. Ron E, Lubin JH, Shore RE, et al. Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies. Radiat Res 1995;141(3):259-77.
96. Pierce DA, Sharp GB, Mabuchi K. Joint effects of radiation and smoking on lung cancer risk among Atomic bomb survivors. Radiat Res 2005;163(6):694-5.
97. Brenner DJ. Does fractionation decrease the risk of breast cancer induced by low-LET radiation? Radiat Res 1999;151(2):225-9.
98. Zahl PH, Strand BH, Maehlen J. Incidence of breast cancer in Norway and Sweden during introduction of nationwide screening: prospective cohort study. Bmj 2004;328(7445):921-4.
99. Hsieh WA, Lucas JN, Hwang JJ, Chan CC, Chang WP. Biodosimetry using chromosomal translocations measured by FISH in a population chronically exposed to low dose-rate 60Co gamma-irradiation. Int J Radiat Biol 2001;77(7):797-804.