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癌症风险和由复制错误和外部因素引起的突变积累的数学模型
Kouki Uchinomiya1, Masanori Tomita1
1Biology and Environmental Chemistry Division, Sustainable System Research Laboratory, Central Research Institute of Electric Power Industry, Komae, Tokyo, Japan.
PloS one
|June 14, 2023
概括
癌症风险受复制错误和变异原体的影响. 一个数学模型表明,仅仅是复制错误就能解释一些癌症类型,但对于其他癌症,如肺癌,变异原体对于生物可信性至关重要.
科学领域:
- 癌症研究 癌症研究
- 数学生物学 数学生物学
- 遗传学 遗传学 是一个
背景情况:
- 终身癌症风险受到由复制错误和暴露于变异原体引起的突变的影响.
- 低剂量辐射暴露对癌症风险的影响仍然不清楚,因为其微妙的影响.
- 数学建模提供了一种方法来评估变异原体的最小影响,通过比较它们存在和不存在的状态.
研究的目的:
- 构建一个数学模型来评估复制错误和变异原体对癌症风险的贡献.
- 为了确定癌症注册数据是否只能通过复制错误来解释.
- 调查变异原体的影响,特别是在复制错误无法完全解释癌症风险的情况下.
主要方法:
- 开发了一种数学模型,将复制错误在细胞分裂过程中的概率和突变原体诱导的突变率纳入其中.
- 基于细胞池容量和细胞死亡的模型细胞分裂停止和恢复.
- 在癌症驱动基因中假定的随机突变,癌症发生在突变值以上.
- 从错误和变异原体中估计的突变数量,以及分析的癌症注册数据.
主要成果:
- 仅仅复制错误就解释了食道,肝脏,甲状腺,胰腺,结肠,乳腺和前列腺癌的风险,但不是白血病.
- 一些癌症 (如肺癌) 的估计参数与仅考虑复制错误时的先前发现不一致.
- 引入变异原影响改善了肺癌的参数估计,使它们更接近报告值.
- 该模型预测,变种原体的影响在具有更高的周转率和更少的癌症发生所需的驱动基因突变的组织中更明显.
结论:
- 对几种癌症类型来说,复制错误是致癌的一个重要因素.
- 变异原体在解释癌症风险方面发挥着至关重要的作用,特别是在肺癌等癌症以及特定的生物环境中.
- 整合复制错误和变异原体效应,为癌症发展提供了更具生物学可信性的解释.
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