Institute of Radiation Medicine, Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764, Neuherberg, Germany.
International Atomic Energy Agency, IAEA Laboratories, Friedensstraße 1, 2444, Seibersdorf, Austria.
Radiat Environ Biophys. 2023 Mar;62(1):1-15. doi: 10.1007/s00411-022-01012-1. Epub 2023 Jan 12.
The probability that an observed cancer was caused by radiation exposure is usually estimated using cancer rates and risk models from radioepidemiological cohorts and is called assigned share (AS). This definition implicitly assumes that an ongoing carcinogenic process is unaffected by the studied radiation exposure. However, there is strong evidence that radiation can also accelerate an existing clonal development towards cancer. In this work, we define different association measures that an observed cancer was newly induced, accelerated, or retarded. The measures were quantified exemplarily by Monte Carlo simulations that track the development of individual cells. Three biologically based two-stage clonal expansion (TSCE) models were applied. In the first model, radiation initiates cancer development, while in the other two, radiation has a promoting effect, i.e. radiation accelerates the clonal expansion of pre-cancerous cells. The parameters of the TSCE models were derived from breast cancer data from the atomic bomb survivors of Hiroshima and Nagasaki. For exposure at age 30, all three models resulted in similar estimates of AS at age 60. For the initiation model, estimates of association were nearly identical to AS. However, for the promotion models, the cancerous clonal development was frequently accelerated towards younger ages, resulting in associations substantially higher than AS. This work shows that the association between a given cancer and exposure in an affected person depends on the underlying biological mechanism and can be substantially larger than the AS derived from classic radioepidemiology.
观察到的癌症是否由辐射暴露引起的概率通常使用来自放射流行病学队列的癌症发病率和风险模型来估计，称为分配份额 (AS)。 这种定义隐含地假设正在进行的致癌过程不受研究辐射暴露的影响。 然而，有强有力的证据表明辐射也可以加速现有的克隆发展为癌症。 在这项工作中，我们定义了观察到的癌症是新诱导的、加速的还是延迟的不同关联度量。 通过跟踪单个细胞发育的蒙特卡罗模拟，对这些度量进行了定量。 应用了三种基于生物学的两阶段克隆扩展 (TSCE) 模型。 在第一个模型中，辐射引发癌症的发生，而在其他两个模型中，辐射具有促进作用，即辐射加速了癌前细胞的克隆扩展。 TSCE 模型的参数是从广岛和长崎原子弹幸存者的乳腺癌数据中推导出来的。 对于 30 岁时的暴露，所有三个模型在 60 岁时得出的 AS 估计值相似。 对于起始模型，关联的估计值几乎与 AS 相同。 然而，对于促进模型，癌变的克隆发展常常加速到更年轻的年龄，导致关联值远高于 AS。 这项工作表明，受影响个体中特定癌症与暴露之间的关联取决于潜在的生物学机制，并且可以大大高于经典放射流行病学得出的 AS。
