The Age Distribution of Cancer: Implications for Models of Carcinogenesis
The Age Distribution of Cancer: Implications for Models of Carcinogenesis
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癌症的年龄分布：对致癌模型的影响
DOI：
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发表时间：
1971
期刊：
影响因子：
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通讯作者：
R. Doll
中科院分区：
文献类型：
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作者：
R. Doll
1.1.十年前，在一篇关于“致癌作用的随机模型”的论文的导言中，阿米蒂奇和我注意到，已经提出了各种各样的模型，没有一个得到普遍接受，也没有一个明确的证据可以排除任何一个进一步考虑（阿米蒂奇和多尔，1961）。这是相当令人沮丧的，但出于两个原因，对这一专题保持兴趣似乎是合理的。首先，模型所依据的许多概念是研究人员在实验基础上提出的，没有用数学术语表述，只有询问这些模型是否满足数据的定量和定性方面才是明智的。其次，为满足定量数据而提出的数学概念可能会为实验提供新的思路。1.2.在此期间，进展缓慢，但我们为我们的兴趣提出的理由仍然有效，而且确实得到了加强。产生癌症的机制仍然是一个推测的问题，但可以考虑几种新的可能性。例如，Bullough和Lawrence（1960）已经获得了一个控制论系统的证据，在这个系统中，细胞释放的物质只作用于同一类型组织中的细胞，并抑制它们的分裂。在这种情况下，累积的基因损伤可能会产生一种不能对抑制物质作出反应的细胞（Bullough，1967）。另一种可能性是，在某些情况下，负责消除外来蛋白质的细胞可能会与人体自身的细胞发生反应。因此，伯内特（1967，1970）假设，这些免疫反应随着年龄的增长而失败，这要么是因为免疫细胞被突变破坏，要么是因为它们能够进行的分裂总数有限（Hayflick，1965）。当这种情况发生时，由基因突变产生的细胞异常能够存活，如果它们具有选择性优势，就会繁殖产生癌症。1.3.在过去的十年中，也出现了更多的定量数据，特别是与人类癌症发病率有关的数据。这些数据有两种类型：癌症登记数据，记录不同类型癌症的发病率，
1.1. TEN years ago in the introduction to a paper on "Stochastic Models for Carcinogenesis" Armitage and I noted that a variety of models had been put forward, none of which had gained general acceptance, and that no clear body of evidence had been marshalled which would exclude any of them from further consideration (Armitage and Doll, 1961). This was rather discouraging, but it seemed reasonable to maintain an interest in the topic for two reasons. Firstly, many of the concepts on which the models had been based were put forward by research workers on experimental grounds without being formulated in mathematical terms, and it was only sensible to enquire whether these models satisfied the quantitative as well as the qualitative aspects of the data. Secondly, it was possible that the mathematical concepts that were evoked to satisfy the quantitative data might suggest new lines for experimentation. 1.2. In the intervening period, progress has been slow, but the reasons we gave for our interest are still valid and, indeed, have been strengthened. The mechanism by which cancers are produced is still a matter for speculation, but several new possibilities can be considered. Bullough and Lawrence (1960), for example, have obtained evidence of a cybernetic system in which substances are released by cells which act only on cells in the same type of tissue and inhibit their division. In this situation accumulated gene damage might produce a cell that was incapable of reacting to the inhibiting substance (Bullough, 1967). Another possibility was suggested by the discovery that the cells responsible for eliminating foreign proteins might, in some circumstances, react with the body's own cells. Burnet (1967, 1970), therefore, postulates that these immunological reactions fail with increasing age, either because the immunological cells are damaged by mutations or because the total number of divisions, of which they are capable, is limited (Hayflick, 1965). When this happens cellular anomalies, themselves produced by gene mutation, are able to survive and if they have a selective advantage, multiply to produce a cancer. 1.3. During the past ten years many more quantitative data have also become available, relating particularly to the incidence of cancer in man. These data are of two types: cancer registry data recording the incidence of different types of cancer by