癌症病因。组织间癌症风险的差异可由干细胞分裂次数来解释。
Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions.
作者信息
Tomasetti Cristian, Vogelstein Bert
机构信息
Division of Biostatistics and Bioinformatics, Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine and Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, 550 North Broadway, Baltimore, MD 21205, USA.
Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, 1650 Orleans Street, Baltimore, MD 21205, USA.
出版信息
Science. 2015 Jan 2;347(6217):78-81. doi: 10.1126/science.1260825.
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.
某些组织类型引发人类癌症的几率比其他组织类型高出数百万倍。尽管这一现象已被认识超过一个世纪，但从未得到解释。在此，我们表明，许多不同类型癌症的终生风险与维持该组织内稳态的正常自我更新细胞的总分裂数密切相关（0.81）。这些结果表明，组织间癌症风险差异中只有三分之一可归因于环境因素或遗传易感性。大部分是由于“运气不佳”，即在正常非癌干细胞的DNA复制过程中发生的随机突变。这不仅对于理解该疾病很重要，而且对于设计降低其所致死亡率的策略也很重要。
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