Frank Steven A
Department of Ecology and Evolutionary Biology, University of California, Irvine, CA 92697, USA.
Curr Biol. 2004 Feb 3;14(3):242-6. doi: 10.1016/j.cub.2003.12.026.
One of the great challenges of cancer research is to explain the epidemiological patterns of cancer incidence based on the molecular processes that lead to uncontrolled cellular proliferation. The epidemiological data demonstrate that the age-specific incidence of many cancers increases in an approximately linear way with age when plotted on a log-log scale, with different slopes for different cancers. However, those epidemiological data also show that cancers of various tissues depart from log-log linearity in particular ways. Here, I illustrate those departures from log-log linearity by introducing plots of the age-specific acceleration of cancer. I then develop a very general model of cancer progression, which I use to explain the observed differences between tissues in age-specific acceleration. In one application of the model, I show that the spectacular rise and fall in age-specific acceleration observed in prostate cancer may be explained by multiple rounds of clonal expansion. In a second application, I demonstrate that the steady decline in age-specific acceleration of breast cancer may occur because precancerous mutations accumulate in many cellular lineages.
癌症研究面临的重大挑战之一，是基于导致细胞不受控制地增殖的分子过程来解释癌症发病率的流行病学模式。流行病学数据表明，许多癌症的年龄特异性发病率在对数-对数尺度上绘制时，随年龄以近似线性的方式增加，不同癌症的斜率不同。然而，这些流行病学数据还表明，不同组织的癌症以特定方式偏离对数-对数线性关系。在此，我通过引入癌症年龄特异性加速的图表来说明这些偏离对数-对数线性关系的情况。然后，我建立了一个非常通用的癌症进展模型，用于解释不同组织在年龄特异性加速方面观察到的差异。在该模型的一个应用中，我表明在前列腺癌中观察到的年龄特异性加速的显著上升和下降可能是由多轮克隆扩增所解释的。在第二个应用中，我证明乳腺癌年龄特异性加速的稳步下降可能是由于癌前突变在许多细胞谱系中积累所致。
