The two "hit" and multiple "hit" theories of carcinogenesis.
The two "hit" and multiple "hit" theories of carcinogenesis.
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DOI：
10.1038/bjc.1969.41
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发表时间：
1969-06
影响因子：
8.8
通讯作者：
Ashley, D J
中科院分区：
文献类型：
--
作者：
Ashley, D J
NORDLING（1953）从美国、英国、法国和挪威公布的统计数据中检查了所有地区的年龄特异性癌症死亡率，并指出肿瘤死亡率随年龄的六次方而上升。他认为癌症的发生可能取决于受影响细胞中的一系列突变，而临床表现则取决于这一系列突变的累积效应。Stocks（1963）研究了一系列队列的男性胃癌死亡率，并得出结论，观察到的模式可以解释为存在一系列5种突变和约17年的临床前发展期。Armitage和Doll（1954）对一些肿瘤的死亡率进行了详细分析，并表明细胞结构和功能的少量随机离散变化的假设如何解释可观察到的癌症死亡率随年龄的稳步上升。三年后（Armitage和Doll，1957），他们发表了另一种分析，认为观察到的死亡率可以根据”两次打击”理论来解释;细胞功能只有两种变化，第一种涉及细胞增殖率的提高，第二种是从控制中释放出来。相关的数学表达式阿米蒂奇和娃娃得出的是：
NORDLING (1953) examined the age specific mortality for cancer of all sites from the published statistics of the United States, the United Kingdom, France and Norway and noted that the tumour death rate rose with the sixth power of the age. He suggested the carcinogenesis might depend on a series of mutations in the affected cells and that the clinical manifestation was dependent on the cumulative effect of this series of mutations. Stocks (1963) examined the mortality rates for gastric cancer in males for a series of cohorts and reached the conclusion that the pattern observed could be explained on the basis that there was a series of 5 mutations and a preclinicaldevelopment period of about 17 years. Armitage and Doll (1954) made a detailed analysis of the death rates for a number of tumours and showed how the hypothesis of a small number of random discrete changes in cell structure and function could account for the observable steady rise in cancer mortality with age. Three years later (Armitage and Doll, 1957) they published an alternative analysis which suggested that the observed death rates could be explained on the basis of a" two hit" theory; that only two changes in cell function, the first involving enhancement ofthe rate of multiplication of cells and the second release from control, were necessary. The relevant mathematical expressions which Armitage and Doll derived were: