MUTATION AND CHILDHOOD CANCER - PROBABILISTIC MODEL FOR INCIDENCE OF RETINOBLASTOMA
MUTATION AND CHILDHOOD CANCER - PROBABILISTIC MODEL FOR INCIDENCE OF RETINOBLASTOMA
复制标题
DOI：
10.1073/pnas.72.12.5116
复制
发表时间：
1975-01-01
影响因子：
11.1
通讯作者：
BROWN, BW
中科院分区：
文献类型：
--
作者：
KNUDSON, AG;HETHCOTE, HW;BROWN, BW
一些儿童癌症的发病率已被证明符合癌症起始的两个突变假说。根据这一假说，第一个突变可以是胚性的或体细胞的，而第二个总是体细胞的。一个概率模型，涉及每个遗传易感个体的肿瘤的平均数作为年龄的函数，并与年龄的视网膜母细胞瘤的发病率数据进行比较。肿瘤平均数量随时间的变化可以用视网膜细胞的生长来解释。在遗传上不易感的患者中，第一和第二体细胞突变的发生时间可以从家族性和非家族性单侧病例发生率的比较中推断。遗传性和非遗传性视网膜母细胞瘤的总发病率与基因和体细胞突变率有关。某些儿童癌症在全世界的平均分布表明，它们的发病率是由自发突变率决定的，而不是由当地环境的诱变致癌物决定的。
The incidences of some childhood cancers have been shown to fit a two-mutation hypothesis for cancer initiation. According to this hypothesis, the first mutation can be either germinal or somatic while the second is always somatic. A probabilistic model involving the mean number of tumors per genetically susceptible individual is developed as a function of age and is compared with age incidence data for retinoblastoma. The change in the mean number of tumors with time is interpreted in terms of the growth of retinal cells. In patients who are not genetically susceptible, the times of occurrence of the first and second somatic mutations can be inferred from a comparison of familial and non-familial unilateral case incidences. The total incidences of hereditary and nonhereditary forms of retinoblastoma are related to germinal and somatic mutation rates. The even distribution of certain childhood cancers throughout the world suggests that their incidences are determined by spontaneous mutation rates rather than by local environmental mutagenic carcinogens.