Stochastic modelling of colon cancer: is there a role for genomic instability?
Stochastic modelling of colon cancer: is there a role for genomic instability?
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DOI：
10.1093/carcin/bgl173
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发表时间：
2007-02-01
期刊：
影响因子：
4.7
通讯作者：
Li, Guangquan
中科院分区：
文献类型：
--
作者：
Little, Mark P.;Li, Guangquan
Little 和 Wright 最近开发了三种基因组不稳定性随机模型（Math. Biosci., (2003) 183, 111-34），具有两个、三个和五个阶段，以及 Nowak 等人的两阶段基因组不稳定性模型。 (Proc. Natl Acad. Sci. USA, (2002) 99, 16226-16231) 与 Luebeck 和 Moolgavkar 提出的四阶段模型 (Proc. Natl Acad. Sci. USA, (2002) 99, 15095-15100) 进行了比较，后者没有假设这种不稳定机制。所有模型均符合美国结肠癌发病率数据。最佳拟合模型是 Nowak 等人的两阶段模型。以及Little和Wright的两级模型，Luebeck和Moolgavkar的四级模型也没有明显逊色。三阶段模型和五阶段模型的拟合度稍差（P < 0.05），五阶段模型拟合度特别差（P < 0.01）。两种最佳基因组不稳定模型都预测，无论性别，基因组不稳定后的细胞突变率至少高出 10000 倍。因此，本文的结果与 Little 和 Wright 之前的分析结果有些出入，表明在结肠癌诱导过程中基因组失稳不发挥作用的模型与那些承担基因组失稳作用的模型可以获得同样好的拟合效果。
Three stochastic models of genomic instability recently developed by Little and Wright (Math. Biosci., (2003) 183, 111-34), with two, three and five stages, and the two-stage genomic instability model of Nowak et al. (Proc. Natl Acad. Sci. USA, (2002) 99, 16226-16231) are compared with the four-stage model proposed by Luebeck and Moolgavkar (Proc. Natl Acad. Sci. USA, (2002) 99, 15095-15100) that does not assume such an instability mechanism. All models are fitted to US colon cancer incidence data. The best fitting models are the two-stage model of Nowak et al. and the two-stage model of Little and Wright, with the four-stage model of Luebeck and Moolgavkar not markedly inferior. The fits of the three-stage and five-stage models are somewhat worse (P < 0.05), the five-stage model fitting particularly poorly (P < 0.01). Both optimal genomic instability models predict cellular mutation rates that are at least 10 000 times higher after genomic destabilization, for both sexes. Therefore, the results of this paper are somewhat at variance with those of previous analyses of Little and Wright in suggesting that equivalently good fit may be obtained by models that do not assume a role for genomic destabilization in the induction of colon cancer as for those that do.