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


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.


Environment Epidemiology Cancer Somatic mutations Risk factors 



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.


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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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