Center for Radiological Research, Department of Radiation Oncology, Columbia University Medical Center, New York, NY, USA.
J Natl Cancer Inst. 2010 Nov 3;102(21):1628-36. doi: 10.1093/jnci/djq346. Epub 2010 Oct 25.
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.
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.
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.
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.
流行病学数据显示，与老年时的辐射暴露相比，儿童时期的辐射暴露与更大的癌症风险相关。然而，对于成年时期的暴露，日本原子弹幸存者中因辐射引起的癌症的相对风险通常不会随着成年暴露年龄的增加而单调下降。这些观察结果与大多数标准的辐射致癌模型不一致，这些模型预测，在所有年龄段，随着暴露年龄的增加，相对风险会单调下降。
我们通过使用一种基于生物学的定量辐射致癌模型来分析日本原子弹幸存者中暴露年龄与观察到的癌症风险模式之间的关系，该模型同时考虑了辐射诱导的癌前细胞形成（启动）和辐射诱导的癌前损伤促进（促进）。这种方法强调了辐射诱导启动和促进的动力学，并跟踪了辐射暴露前后、期间、短期和长期后癌前细胞的产量。
年轻个体暴露后的辐射风险主要由启动过程决定，而老年个体暴露后的辐射风险则更多地受到现有癌前细胞促进的影响。因此，癌症部位之间启动和促进的平衡决定了癌症风险对辐射暴露年龄的依赖性。例如，就辐射诱导的癌前细胞而言，启动与促进之间的相对贡献的定量衡量标准，乳腺癌是肺癌的 10 倍。反映了这种差异，辐射诱导的乳腺癌风险随着暴露年龄的增加而降低，而辐射诱导的肺癌风险则不会。
对于中年时期的辐射暴露，大多数辐射诱导的癌症风险并不像通常假设的那样随着暴露年龄的增加而降低。这一观察结果表明，随着暴露年龄的增加，辐射致癌中的促进过程变得越来越重要。中年时期暴露后的辐射诱导癌症风险可能比之前估计的高出一倍，这可能对职业暴露和放射成像产生影响。
