Oncogene：揭示为何癌症发病率随着年龄增长而增加

近日，来自科罗拉多大学癌症中心的一篇研究综述揭示了癌症是和年龄相关的，癌症在老年人中的发病频率比在年轻人中高许多。相关研究成果刊登在了国际杂志Oncogene上，文章中研究者反对传统的观点，传统观点认为老年人癌症发生是由于引发癌症突变的积累所导致的。

组织纹理的改变和非必要的致癌突变的积累可以驱动老年人的高癌症风险

研究者James表示，如今的米克-贾格尔(Mick Jagger，滚石乐队主唱)和其1960年的对比，你会发现现在的他的机体组织纹理发生了明显的改变。这种改变并不是促使癌症突变因子的积累所导致的，但是其可以促使其癌症发病比率升高。基于证据，研究者首次指出，等我们在我们青少年晚期停止生长的时候，我们已经积累了我们一生的一大群突变，突变曲线和癌症曲线的错配意味着癌症如果已经达到了一个临界点，也就是说5-6个突变，这样我们就会看到20多岁人群高的癌症发病风险。

研究者同样指出，甚至是健康的组织也会有许多致癌的突变。如果癌基因能够围绕在组织周围，那么向老鼠干细胞中引入癌基因可以帮助小鼠的组织细胞生存，而且干细胞可以包裹癌基因使得癌基因快速被淘汰。

我们健康的细胞会达到最优化状态来完成维持机体健康的任务，如果改变了这种平衡，比如发生致癌的突变，那么机体中的健康细胞便会迅速反应战胜致癌突变的细胞。但是如果组织变老了，健康细胞便不能完美胜任机体赋予其的责任了，此时突变或许会帮助癌细胞来适应机体，发生癌症。

编译自：Why cancer rate increases with age (it's not what you think)

doi:10.1038/onc.2012.281
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Challenging the axiom: does the occurrence of oncogenic mutations truly limit cancer development with age?

J DeGregori

A widely accepted paradigm in cancer research holds that the development of cancers is rate limited by the occurrence of oncogenic mutations. In particular, the exponential rise in the incidence of most cancers with age is thought to reflect the time required for cells to accumulate the multiple oncogenic mutations needed to confer the cancer phenotype. Here I will argue against the axiom that the occurrence of oncogenic mutations limits cancer incidence with age, based on several observations, including that the rate of mutation accumulation is maximal during ontogeny, oncogenic mutations are frequently detected in normal tissues, the evolution of complex multicellularity was not accompanied by reductions in mutation rates, and that many oncogenic mutations have been shown to impair stem cell activity. Moreover, although evidence that has been used to support the current paradigm includes increased cancer incidence in individuals with inherited DNA repair deficiencies or exposed to mutagens, the pleotropic effects of these contexts could enhance tumorigenesis at multiple levels. I will further argue that age-dependent alteration of selection for oncogenic mutations provides a more plausible explanation for increased cancer incidence in the elderly. Although oncogenic mutations are clearly required for cancer evolution, together these observations counter the common view that age dependence of cancers is largely explained by the time required to accumulate sufficient oncogenic mutations.