Boice J D, Blettner M, Kleinerman R A, Stovall M, Moloney W C, Engholm G, Austin D F, Bosch A, Cookfair D L, Krementz E T, Latourette H B, Peters L J, Schulz M D, Lundell M, Pettersson F, Storm H H, Bell C M, Coleman M P, Fraser P, Palmer M, Prior P, Choi N W, Hislop T G, Koch M, Robb D, Robson D, Spengler R F, von Fournier D, Frischkorn R, Lochmüller H, Pompe-Kirn V, Rimpela A, Kjørstad K, Pejovic M H, Sigurdsson K, Pisani P, Kucera H, Hutchison G B
Radiation Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892.
J Natl Cancer Inst. 1987 Dec;79(6):1295-311.
To quantify the risk of radiation-induced leukemia and provide further information on the nature of the relationship between dose and response, a case-control study was undertaken in a cohort of over 150,000 women with invasive cancer of the uterine cervix. The cases either were reported to one of 17 population-based cancer registries or were treated in any of 16 oncologic clinics in Canada, Europe, and the United States. Four controls were individually matched to each of 195 cases of leukemia on the basis of age and calendar year when diagnosed with cervical cancer and survival time. Leukemia diagnoses were verified by one hematologist. Radiation dose to active bone marrow was estimated by medical physicists on the basis of the original radiotherapy records of study subjects. The risk of chronic lymphocytic leukemia, one of the few malignancies without evidence for an association with ionizing radiation, was not increased [relative risk (RR) = 1.03; n = 52]. However, for all other forms of leukemia taken together (n = 143), a twofold risk was evident (RR = 2.0; 90% confidence interval = 1.0-4.2). Risk increased with increasing radiation dose until average doses of about 400 rad (4 Gy) were reached and then decreased at higher doses. This pattern is consistent with experimental data for which the down-turn in risk at high doses has been interpreted as due to killing of potentially leukemic cells. The dose-response information was modeled with various RR functions, accounting for the nonhomogeneous distribution of radiation dose during radiotherapy. The local radiation doses to each of 14 bone marrow compartments for each patient were incorporated in the models, and the corresponding risks were summed. A good fit to the observed data was obtained with a linear-exponential function, which included a positive linear induction term and a negative exponential term. The estimate of the excess RR per rad was 0.9%, and the estimated RR at 100 rad (1 Gy) was 1.7. The model proposed in this study of risk proportional to mass exposed and of risk to an individual given by the sum of incremental risks to anatomic sites appears to be applicable to a wide range of dose distributions. Furthermore, the pattern of leukemia incidence associated with different levels of radiation dose is consistent with a model postulating increasing risk with increasing exposure, modified at high doses by increased frequency of cell death, which reduces risk.
为了量化辐射诱发白血病的风险，并提供关于剂量与反应关系本质的更多信息，在一个超过15万名浸润性宫颈癌女性队列中开展了一项病例对照研究。这些病例要么被报告给17个基于人群的癌症登记处之一，要么在加拿大、欧洲和美国的16家肿瘤诊所之一接受治疗。根据年龄、确诊宫颈癌时的历年时间以及生存时间，为195例白血病病例中的每一例分别匹配了4名对照。白血病诊断由一名血液学家进行核实。医学物理学家根据研究对象的原始放疗记录估算了对活跃骨髓的辐射剂量。慢性淋巴细胞白血病是少数几种无证据表明与电离辐射有关联的恶性肿瘤之一，其风险并未增加[相对风险（RR）=1.03；n=52]。然而，对于其他所有类型白血病合并在一起的情况（n=143），两倍的风险是明显的（RR=2.0；90%置信区间=1.0 - 4.2）。风险随着辐射剂量的增加而增加，直到达到约400拉德（4戈瑞）的平均剂量，然后在更高剂量时下降。这种模式与实验数据一致，在实验数据中，高剂量时风险的下降被解释为由于潜在白血病细胞的死亡。剂量反应信息用各种RR函数进行建模，考虑了放疗期间辐射剂量的非均匀分布。将每位患者14个骨髓区室的局部辐射剂量纳入模型，并对相应风险进行求和。用线性 - 指数函数获得了与观察数据的良好拟合，该函数包括一个正的线性诱导项和一个负的指数项。每拉德的超额RR估计值为0.9%，100拉德（1戈瑞）时的估计RR为1.7。本研究中提出的风险与暴露质量成正比以及个体风险由解剖部位增量风险之和给出的模型似乎适用于广泛的剂量分布。此外，与不同辐射剂量水平相关的白血病发病率模式与一个模型一致，该模型假定随着暴露增加风险增加，在高剂量时因细胞死亡频率增加而改变，从而降低风险。
