Cancer Risks After Radiation Exposure in Middle Age
Cancer Risks After Radiation Exposure in Middle Age
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DOI：
10.1093/jnci/djq346
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发表时间：
2010-11-01
影响因子：
10.3
通讯作者：
Brenner, David J.
中科院分区：
文献类型：
--
作者：
Shuryak, Igor;Sachs, Rainer K.;Brenner, David J.
背景流行病学数据表明，与老年时期的辐射暴露相比，儿童时期的辐射暴露与更大的癌症风险相关。然而，就成年期的照射而言，日本原子弹爆炸幸存者中辐射诱发癌症的相对风险一般不会随着成年期受照射年龄的增加而单调下降。这些观察结果与辐射诱发癌症的大多数标准模型不一致，后者预测相对风险随着受照年龄的增加而单调下降，方法我们使用一个基于生物学的辐射致癌作用的定量模型，分析了在日本原子弹爆炸幸存者中观察到的癌症风险模式作为暴露年龄的函数，该模型包括癌前细胞的辐射诱导，（起始）和辐射诱导的癌前损害的促进。这种方法强调辐射诱导的启动和促进的动力学，并跟踪前癌细胞的产量之前，期间，不久后，和长期后，辐射exposure.Results辐射风险暴露后，在年轻的个人为主的启动过程，而辐射风险暴露后，在以后的年龄更受影响的促进预先存在的癌前细胞。因此，癌症发生和发展之间的依赖于癌症部位的平衡决定了癌症风险对辐射照射时年龄的依赖性。例如，就癌前细胞的辐射诱导而言，乳腺癌的起始与促进的相对贡献的定量测量比肺癌大10倍。反映这种差异，辐射引起的乳腺癌的风险随着年龄的暴露在所有年龄，而辐射引起的肺癌的风险没有。结论在中年的辐射暴露，大多数辐射引起的癌症的风险不，因为通常假设，随着年龄的增加而减少暴露。这一观察结果表明，随着受照年龄的增加，辐射致癌作用的促进过程变得越来越重要。中年人受照射后辐射诱发癌症的风险可能高达先前估计的两倍，这可能对职业照射和放射成像产生影响。
Background Epidemiological data show that radiation exposure during childhood is associated with larger cancer risks compared with exposure at older ages. For exposures in adulthood, however, the relative risks of radiation-induced cancer in Japanese atomic bomb survivors generally do not decrease monotonically with increasing age of adult exposure. These observations are inconsistent with most standard models of radiation-induced cancer, which predict that relative risks decrease monotonically with increasing age at exposure, at all ages.Methods We analyzed observed cancer risk patterns as a function of age at exposure in Japanese atomic bomb survivors by using a biologically based quantitative model of radiation carcinogenesis that incorporates both radiation induction of premalignant cells (initiation) and radiation-induced promotion of premalignant damage. This approach emphasizes the kinetics of radiation-induced initiation and promotion, and tracks the yields of premalignant cells before, during, shortly after, and long after radiation exposure.Results Radiation risks after exposure in younger individuals are dominated by initiation processes, whereas radiation risks after exposure at later ages are more influenced by promotion of preexisting premalignant cells. Thus, the cancer site-dependent balance between initiation and promotion determines the dependence of cancer risk on age at radiation exposure. For example, in terms of radiation induction of premalignant cells, a quantitative measure of the relative contribution of initiation vs promotion is 10-fold larger for breast cancer than for lung cancer. Reflecting this difference, radiation-induced breast cancer risks decrease with age at exposure at all ages, whereas radiation-induced lung cancer risks do not.Conclusion For radiation exposure in middle age, most radiation-induced cancer risks do not, as often assumed, decrease with increasing age at exposure. This observation suggests that promotional processes in radiation carcinogenesis become increasingly important as the age at exposure increases. Radiation-induced cancer risks after exposure in middle age may be up to twice as high as previously estimated, which could have implications for occupational exposure and radiological imaging.