Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions.
Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions.
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DOI：
10.1126/science.1260825
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发表时间：
2015-01-02
期刊：
影响因子：
--
通讯作者：
Vogelstein B
中科院分区：
文献类型：
--
作者：
Tomasetti C;Vogelstein B
某些组织类型引起人类癌症的几率是其他组织类型的数百万倍。尽管这一点已经被人们认识了一个多世纪，但从未得到解释。在这里，我们表明，许多不同类型的癌症的终生风险与维持组织稳态的正常自我更新细胞的分裂总数密切相关（0.81）。这些结果表明，组织间癌症风险的变化中只有三分之一可归因于环境因素或遗传倾向。大多数是由于“运气不好”，即正常非癌干细胞 DNA 复制过程中出现的随机突变。这不仅对于了解这种疾病很重要，而且对于设计限制其造成的死亡率的策略也很重要。
Some tissue types give rise to human cancers millions of times more often than other tissue types. Although this has been recognized for more than a century, it has never been explained. Here, we show that the lifetime risk of cancers of many different types is strongly correlated (0.81) with the total number of divisions of the normal self-renewing cells maintaining that tissue's homeostasis. These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to “bad luck,” that is, random mutations arising during DNA replication in normal, noncancerous stem cells. This is important not only for understanding the disease but also for designing strategies to limit the mortality it causes.
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