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Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention
Science ( IF 56.9 ) Pub Date : 2017-03-23 , DOI: 10.1126/science.aaf9011 Cristian Tomasetti 1, 2 , Lu Li 2 , Bert Vogelstein 3
Science ( IF 56.9 ) Pub Date : 2017-03-23 , DOI: 10.1126/science.aaf9011 Cristian Tomasetti 1, 2 , Lu Li 2 , Bert Vogelstein 3
Affiliation
A substantial fraction of mutations in human cancer are attributable to random errors occurring during DNA replication. Cancer and the unavoidable R factor Most textbooks attribute cancer-causing mutations to two major sources: inherited and environmental factors. A recent study highlighted the prominent role in cancer of replicative (R) mutations that arise from a third source: unavoidable errors associated with DNA replication. Tomasetti et al. developed a method for determining the proportions of cancer-causing mutations that result from inherited, environmental, and replicative factors (see the Perspective by Nowak and Waclaw). They found that a substantial fraction of cancer driver gene mutations are indeed due to replicative factors. The results are consistent with epidemiological estimates of the fraction of preventable cancers. Science, this issue p. 1330; see also p. 1266 Cancers are caused by mutations that may be inherited, induced by environmental factors, or result from DNA replication errors (R). We studied the relationship between the number of normal stem cell divisions and the risk of 17 cancer types in 69 countries throughout the world. The data revealed a strong correlation (median = 0.80) between cancer incidence and normal stem cell divisions in all countries, regardless of their environment. The major role of R mutations in cancer etiology was supported by an independent approach, based solely on cancer genome sequencing and epidemiological data, which suggested that R mutations are responsible for two-thirds of the mutations in human cancers. All of these results are consistent with epidemiological estimates of the fraction of cancers that can be prevented by changes in the environment. Moreover, they accentuate the importance of early detection and intervention to reduce deaths from the many cancers arising from unavoidable R mutations.
中文翻译:
干细胞分裂、体细胞突变、癌症病因和癌症预防
人类癌症中的很大一部分突变可归因于 DNA 复制过程中发生的随机错误。癌症和不可避免的 R 因素 大多数教科书将致癌突变归因于两个主要来源:遗传因素和环境因素。最近的一项研究强调了由第三个来源引起的复制 (R) 突变在癌症中的突出作用:与 DNA 复制相关的不可避免的错误。托马塞蒂等人。开发了一种确定由遗传、环境和复制因素引起的致癌突变比例的方法(参见 Nowak 和 Waclaw 的观点)。他们发现很大一部分癌症驱动基因突变确实是由复制因素引起的。结果与可预防癌症比例的流行病学估计一致。科学,这个问题 1330; 另见第。1266 癌症是由遗传突变、环境因素诱导或 DNA 复制错误导致的突变引起的 (R)。我们研究了全球 69 个国家的正常干细胞分裂次数与 17 种癌症类型风险之间的关系。数据显示,无论环境如何,所有国家的癌症发病率与正常干细胞分裂之间都存在很强的相关性(中位数 = 0.80)。R 突变在癌症病因学中的主要作用得到了独立方法的支持,该方法完全基于癌症基因组测序和流行病学数据,这表明 R 突变是人类癌症中三分之二突变的原因。所有这些结果都与可以通过环境变化预防的癌症比例的流行病学估计一致。此外,它们强调了早期检测和干预的重要性,以减少由不可避免的 R 突变引起的许多癌症的死亡。
更新日期:2017-03-23
中文翻译:
干细胞分裂、体细胞突变、癌症病因和癌症预防
人类癌症中的很大一部分突变可归因于 DNA 复制过程中发生的随机错误。癌症和不可避免的 R 因素 大多数教科书将致癌突变归因于两个主要来源:遗传因素和环境因素。最近的一项研究强调了由第三个来源引起的复制 (R) 突变在癌症中的突出作用:与 DNA 复制相关的不可避免的错误。托马塞蒂等人。开发了一种确定由遗传、环境和复制因素引起的致癌突变比例的方法(参见 Nowak 和 Waclaw 的观点)。他们发现很大一部分癌症驱动基因突变确实是由复制因素引起的。结果与可预防癌症比例的流行病学估计一致。科学,这个问题 1330; 另见第。1266 癌症是由遗传突变、环境因素诱导或 DNA 复制错误导致的突变引起的 (R)。我们研究了全球 69 个国家的正常干细胞分裂次数与 17 种癌症类型风险之间的关系。数据显示,无论环境如何,所有国家的癌症发病率与正常干细胞分裂之间都存在很强的相关性(中位数 = 0.80)。R 突变在癌症病因学中的主要作用得到了独立方法的支持,该方法完全基于癌症基因组测序和流行病学数据,这表明 R 突变是人类癌症中三分之二突变的原因。所有这些结果都与可以通过环境变化预防的癌症比例的流行病学估计一致。此外,它们强调了早期检测和干预的重要性,以减少由不可避免的 R 突变引起的许多癌症的死亡。