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European Journal of Epidemiology

, Volume 34, Issue 5, pp 439–445 | Cite as

Stem cell replication, somatic mutations and role of randomness in the development of cancer

  • Vittorio Perduca
  • Ludmil B. Alexandrov
  • Michelle Kelly-Irving
  • Cyrille Delpierre
  • Hanane Omichessan
  • Mark P. Little
  • Paolo Vineis
  • Gianluca SeveriEmail author
ESSAY

Abstract

An intense scientific debate has recently taken place relating to the “bad luck” hypothesis in cancer development, namely that intrinsic random, and therefore unavoidable, mutagenic events would have a predominant role in tumorigenesis. In this article we review the main contributions to this debate and explain the reasons why the claim that cancer is mostly explained by intrinsic random factors is unsupported by data and theoretical models. In support of this, we present an analysis showing that smoking-induced mutations are more predictive of cancer risk than the lifetime number of stem cell cellular divisions.

Keywords

Environment Epidemiology Cancer Somatic mutations Risk factors 

Notes

Acknowledgements

We acknowledge the support of a grant to Gianluca Severi on epigenetic signatures and breast cancer from the French Ligue contre le Cancer (Appel à projets 2016 “Recherche en Epidemiologie”). Hanane Omichessan is supported by a PhD fellowship from the French Institut National du Cancer (INCa reference 11330).

Author’s Contribution

GS and PV conceived the study. VP, GS and HO did the review and the figures. All authors designed the study, collected the data, did the statistical analysis, analysed and interpreted the data, wrote and reviewed the manuscript, and approved the final version.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Tomasetti C, Vogelstein B. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science. 2015;347(6217):78–81.  https://doi.org/10.1126/science.1260825.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Tomasetti C, Vogelstein B. Cancer risk: role of environment–response. Science. 2015;347(6223):729–31.  https://doi.org/10.1126/science.aaa6592.CrossRefPubMedGoogle Scholar
  3. 3.
    Tomasetti C, Vogelstein B. Musings on the theory that variation in cancer risk among tissues can be explained by the number of divisions of normal stem cells. 2015. arXiv preprint arXiv:150105035.
  4. 4.
    Tomasetti C, Vogelstein B. On the slope of the regression between stem cell divisions and cancer risk, and the lack of correlation between stem cell divisions and environmental factors-associated cancer risk. PLoS ONE. 2017;12(5):2–5.  https://doi.org/10.1371/journal.pone.0175535.CrossRefGoogle Scholar
  5. 5.
    Tomasetti C, Li L, Vogelstein B. Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention. Science. 2017;355(6331):1330–4.  https://doi.org/10.1126/science.aaf9011.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Ashford NA, Bauman P, Brown HS, et al. Cancer risk: role of environment. Science. 2015;347(6223):727.CrossRefGoogle Scholar
  7. 7.
    Potter JD, Prentice RL. Cancer risk: tumors excluded. Science. 2015;347(6223):727.CrossRefGoogle Scholar
  8. 8.
    Wild C, Brennan P, Plummer M, Bray F, Straif K, Zavadil J. Cancer risk: role of chance overstated. Science. 2015;347(6223):728.CrossRefGoogle Scholar
  9. 9.
    Gotay C, Dummer T, Spinelli J. Cancer risk: prevention is crucial. Science. 2015;347(6223):728.CrossRefGoogle Scholar
  10. 10.
    Song M, Giovannucci EL. Cancer risk: many factors contribute. Science. 2015;347(6223):728–9.  https://doi.org/10.1126/science.aaa6094.CrossRefPubMedGoogle Scholar
  11. 11.
    O’Callaghan M. Cancer risk: accuracy of literature. Science. 2015;347(6223):729.CrossRefGoogle Scholar
  12. 12.
    IACR. Press Release No. 231. 13 January 2015. Most types of cancer not due to “bad luck” IARC responds to scientific article claiming that environmental and lifestyle factors account for less than one third of cancers. Cent Eur J Public Health. 2015;23(1):87.  https://doi.org/10.1126/science.1260825.CrossRefGoogle Scholar
  13. 13.
    Weinberg CR, Zaykin D. Is bad luck the main cause of cancer? J Natl Cancer Inst. 2015;107(7):1–4.  https://doi.org/10.1093/jnci/djv125.CrossRefGoogle Scholar
  14. 14.
    Wu S, Powers S, Zhu W, Hannun YA. Substantial contribution of extrinsic risk factors to cancer development. Nature. 2015;529(7584):43–7.  https://doi.org/10.1038/nature16166.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Agudo A, Bonet C, Travier N, et al. Impact of cigarette smoking on cancer risk in the European prospective investigation into cancer and nutrition study. J Clin Oncol. 2012;30(36):4550–7.  https://doi.org/10.1200/JCO.2011.41.0183.CrossRefPubMedGoogle Scholar
  16. 16.
    Giovannucci EL. Are most cancers caused by specific risk factors acting on tissues with high underlying stem cell divisions? J Natl Cancer Inst. 2016;108(3):9–11.  https://doi.org/10.1093/jnci/djv343.CrossRefGoogle Scholar
  17. 17.
    Podolskiy DI, Gladyshev VN. Intrinsic versus extrinsic cancer risk factors and aging. Trends Mol Med. 2016;22(10):833–4.  https://doi.org/10.1016/j.molmed.2016.08.001.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Krieger N. Health equity and the fallacy of treating causes of population health as if they sum to 100%. Am J Public Health. 2017;107(4):541–9.  https://doi.org/10.2105/AJPH.2017.303655.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    De Martel C, Ferlay J, Franceschi S, et al. Global burden of cancers attributable to infectins in 2008: a review and synthetic analysis. Lancet. 2012;379(9829):1851.  https://doi.org/10.1016/S1470-2045(12)70137-7.CrossRefGoogle Scholar
  20. 20.
    Kelly-Irving M, Delpierre C, Vineis P. Beyond bad luck: induced mutations and hallmarks of cancer. Lancet Oncol. 2017;18(8):999–1000.  https://doi.org/10.1016/S1470-2045(17)30520-X.CrossRefPubMedGoogle Scholar
  21. 21.
    Kim R, Emi M, Tanabe K. Cancer immunoediting from immune surveillance to immune escape. Immunology. 2007;121(1):1–14.CrossRefGoogle Scholar
  22. 22.
    Stewart TJ, Abrams SI. How tumours escape mass destruction. Oncogene. 2008;27(45):5894–903.  https://doi.org/10.1038/onc.2008.268.CrossRefPubMedGoogle Scholar
  23. 23.
    Huang SXL, Jaurand MC, Kamp DW, Whysner J, Hei TK. Role of mutagenicity in asbestos fiber-induced carcinogenicity and other diseases. J Toxicol Environ Heal Part B Crit Rev. 2011;14(1–4):179–245.  https://doi.org/10.1080/10937404.2011.556051.CrossRefGoogle Scholar
  24. 24.
    Alexandrov LB, Nik-Zainal S, Wedge DC, et al. Signatures of mutational processes in human cancer. Nature. 2013;500(7463):415–21.  https://doi.org/10.1038/nature12477.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Perduca V, Omichessan H, Baglietto L, Severi G. Mutational and epigenetic signatures in cancer tissue linked to environmental exposures and lifestyle. Curr Opin Oncol. 2018;30(1):61–7.  https://doi.org/10.1097/CCO.0000000000000418.CrossRefPubMedGoogle Scholar
  26. 26.
    Watson HW, Galton F. On the probability of the extinction of families. J Anthropol Inst G B Irel. 1875;4:138–44.  https://doi.org/10.2307/2841222.CrossRefGoogle Scholar
  27. 27.
    Little MP, Hendry JH. Mathematical models of tissue stem and transit target cell divisions and the risk of radiation- or smoking-associated cancer. PLoS Comput Biol. 2017;13(2):1–29.  https://doi.org/10.1371/journal.pcbi.1005391.CrossRefGoogle Scholar
  28. 28.
    Alexandrov LB, Ju YS, Haase K, et al. Mutational signatures associated with tobacco smoking in human cancer. Science. 2016;354(6312):618–22.  https://doi.org/10.1126/science.aag0299.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Little MP, Hendry JH, Puskin JS. Lack of correlation between stem-cell proliferation and radiation- or smoking-associated cancer risk. PLoS ONE. 2016;11(3):e0150335.  https://doi.org/10.1371/journal.pone.0150335.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Luzzatto L, Pandolfi PP. Causality and chance in the development of cancer. N Engl J Med. 2015;373(1):84–8.  https://doi.org/10.1056/nejmsb1502456.CrossRefPubMedGoogle Scholar
  31. 31.
    Armitage P, Doll R. A two-stage theory of carcinogenesis in relation to the age distribution of human cancer. Br J Cancer. 1957;11(2):161–9.  https://doi.org/10.1038/bjc.1957.22.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Kahneman D, Slovic P, Tversky A. Judgment under uncertainty. Science. 1982;185(4157):1124–31.  https://doi.org/10.1093/oxfordhb/9780195376746.013.0038.CrossRefGoogle Scholar
  33. 33.
    Lucas JE, Sapiro G. Cancer: what’s luck got to do with it? Significance. 2015;12(2):40–2.  https://doi.org/10.1111/j.1740-9713.2015.00816.x.CrossRefGoogle Scholar
  34. 34.
    Treasure P. Cancer: misfortune or carelessness? Significance. 2017;14(5):8–9.  https://doi.org/10.1111/j.1740-9713.2017.01067.x.CrossRefGoogle Scholar
  35. 35.
    Doll R, Peto R, Boreham J, Sutherland I. Mortality from cancer in relation to smoking: 50 years observations on British doctors. Br J Cancer. 2005;92(3):426–9.  https://doi.org/10.1038/sj.bjc.6602359.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Laboratoire de Mathématiques Appliquées MAP5 (UMR CNRS 8145)Université Paris DescartesParisFrance
  2. 2.Department of Cellular and Molecular Medicine and Department of Bioengineering and Moores Cancer CenterUniversity of CaliforniaSan Diego, La JollaUSA
  3. 3.UMR1027INSERMToulouseFrance
  4. 4.UMR1027Université Toulouse III Paul-SabatierToulouseFrance
  5. 5.Radiation Epidemiology BranchNational Cancer InstituteBethesdaUSA
  6. 6.MRC-PHE Centre for Environment and HealthImperial CollegeLondonUK
  7. 7.CESP (Inserm U1018), Facultés de Médicine Université Paris-SudUVSQ, Université Paris-Saclay, Gustave RoussyVillejuifFrance
  8. 8.Cancer Epidemiology CentreCancer Council VictoriaMelbourneAustralia

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