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