Mathematical modeling in carcinogenesis to elucidate the mechanism of radiation-induced cancer

在以往关于辐射相关癌症机制的范式中，由于直接损伤DMA而引起的突变事件可引起起始导致癌症。多阶段建模有助于理解癌症的诱发过程。在最近的多阶段建模研究中，原子弹爆炸幸存者的流行病学数据对辐射致癌分析非常有用。近年来的生物学研究表明，与辐射致癌有关的不是辐射引起的直接突变，而是间接突变。基因组不稳定现象可能改变我们对低剂量和剂量率反应的理解。此外，从辐射生物学的角度验证基因组不稳定性是否有助于致癌，可能会引起很大的兴趣。基因组不稳定假说可以提供辐射致癌的示意图。基于这一假设，将开发考虑基因组不稳定性的致癌模型，并利用广岛和长崎原子弹爆炸幸存者的数据进行分析。如果我们看一下1987年之前原子弹幸存者的数据，基因组不稳定性是否与辐射致癌有关的假设并没有被拒绝。进一步的随访对模型的验证至关重要。

In the previous paradigm for mechanism of radiation-related cancer, mutational events due to direct damage to DMA could cause initiation leading to cancer. Multistage modeling can contribute to an understanding of the induction of cancer. In recent studies on multistage modeling, the epidemiological data of atomic bomb survivors are very useful for analyzing radiation carcinogenesis.Recent biological data indicate that not direct mutation induced by radiation but indirect mutation would be relevant to radiation carcinogenesis. The phenomena of genomic instability may change our understanding of low dose and dose-rate response. In addition, it may be of much interest to verify an implication from radiation biology whether genomic instability contributes to carcinogenesis or not. A genomic instability hypothesis can provide a schematic diagram of radiation carcinogenesis.Based on this hypothesis, carcinogenesis models considering genomic instability will be developed and analyzed using the atomic bomb survivor data in Hiroshima and Nagasaki. The hypothesis whether genomic instability is relevant to radiation carcinogenesis is not rejected if we look at the atomic bomb survivor data until 1987. Further follow-up of the cohort will be essential to validation of the models.