Knudson A G
Am J Pathol. 1974 Oct;77(1):77-84.
The dominantly inherited tumors of man demonstrate that mutation can be a step on the carcinogenetic pathway. Nonhereditary tumors may involve the same mutation in somatic cells rather than germ cells. In neither case is this mutation alone sufficient to produce a tumor, and evidence is presented that a second mutational step is required in the initiation process. Individuals who bear these mutations germinally are extremely susceptible to specific tumors, they may develop more than one tumor, and the average age at onset is earlier than usual. Recessive genes for cancer susceptibility and environmental carcinogens may interact with each other and with these dominant "cancer genes" to increase the probability that cancer mutations will occur.
人类的显性遗传肿瘤表明,突变可能是致癌途径中的一个步骤。非遗传性肿瘤可能在体细胞而非生殖细胞中发生相同的突变。在这两种情况下,这种突变本身都不足以产生肿瘤,并且有证据表明在起始过程中还需要第二个突变步骤。携带这些生殖系突变的个体极易患特定肿瘤,他们可能会患不止一种肿瘤,而且平均发病年龄比通常情况更早。癌症易感性的隐性基因和环境致癌物可能相互作用,并与这些显性“癌症基因”相互作用,以增加癌症突变发生的可能性。