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Role of stem-cell divisions in cancer risk

Nature volume 548, pages E13–E14 (2017)Cite this article

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arising from S. Wu, S. Powers, W. Zhu & Y. A. Hannun Nature 529, 43–47 (2016); doi:10.1038/nature16166

We recently reported a strong correlation between the incidence of cancers and the number of stem-cell divisions in the corresponding normal tissues1. We interpreted this correlation to mean that random genomic alterations (termed replicative or intrinsic) arising during DNA replication, as well as mutations that arise owing to environmental (extrinsic) and inherited factors, have important roles in tumorigenesis1,2,3; however, we did not quantify the contribution of intrinsic versus extrinsic factors to any cancer type1. In their study, Wu et al.4 estimated an upper bound for the contribution of intrinsic factors to many cancer types, concluding that intrinsic factors account for “less than 10–30%” of cancer cases. We believe that several of the assumptions made by these authors led them to underestimate the role of intrinsic factors, and we further show that one of their methods leads to the conclusion that extrinsic factors account for >85% of the risk in situations in which extrinsic factors have no role. There is a Reply to this Comment by Wu, S., Zhu, W. & Hannun, Y. A. Nature 548, 10.1038/nature23303 (2017).

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Figure 1: The effect of different assumptions of extrinsic risk for the upper boundary line.
Figure 2: The effect of noise in stem cell estimates of cancer risk.

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Author information

Authors and Affiliations

  1. Division of Biostatistics and Bioinformatics, Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, 550 North Broadway, Baltimore, 21205, Maryland, USA

    Cristian Tomasetti

  2. Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, 21205, Maryland, USA

    Cristian Tomasetti

  3. Department of Mathematics, Duke University, Durham, 27708, North Carolina, USA

    Rick Durrett

  4. Department of Statistics, Rice University, Houston, 77005, Texas, USA

    Marek Kimmel

  5. Laboratoire de Probabilités & Modéles Aléatoires, UMPC Université Paris 06, 75252, Paris, France

    Amaury Lambert & Giovanni Parmigiani

  6. Department of Biostatistics, Harvard T.H. Chan School of Public Health & Dana-Farber Cancer Institute, Boston, 02115, Massachusetts, USA

    Giovanni Parmigiani

  7. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, 10017, New York, USA

    Ann Zauber

  8. Ludwig Center & Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, 1650 Orleans Street St, Baltimore, 21205, Maryland, USA

    Bert Vogelstein

Authors
  1. Cristian Tomasetti
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  2. Rick Durrett
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  3. Marek Kimmel
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  4. Amaury Lambert
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  5. Giovanni Parmigiani
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  6. Ann Zauber
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  7. Bert Vogelstein
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Contributions

C.T. and B.V. conceived and designed the research. C.T., R.D., M.K., A.L., G.P., A.Z. and B.V. performed related research. C.T. and B.V. wrote the first draft of the article and all authors contributed to the submitted version.

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Correspondence to Cristian Tomasetti.

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The authors declare no competing financial interests.

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Tomasetti, C., Durrett, R., Kimmel, M. et al. Role of stem-cell divisions in cancer risk. Nature 548, E13–E14 (2017). https://doi.org/10.1038/nature23302

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