Variation in cancer risk among tissues can be explained by the number of stem cell divisions

Variation in cancer risk among tissues can be explained by the number of stem cell divisions

1. Cristian Tomasetti1,*, 
2. Bert Vogelstein2,*

+Author Affiliations

1. ¹Division of Biostatistics and Bioinformatics, Department of Oncology, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine and Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, 550 North Broadway, Baltimore, MD 21205, USA.
2. ²Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, 1650 Orleans Street, Baltimore, MD 21205, USA.

1. ↵*Corresponding author. E-mail: ctomasetti@jhu.edu (C.T.); vogelbe@jhmi.edu (B.V.)

• ABSTRACT
• EDITOR'S SUMMARY

Some tissue types give rise to human cancers millions of times more often than other tissue types. Although this has been recognized for more than a century, it has never been explained. Here, we show that the lifetime risk of cancers of many different types is strongly correlated (0.81) with the total number of divisions of the normal self-renewing cells maintaining that tissue’s homeostasis. These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to “bad luck,” that is, random mutations arising during DNA replication in normal, noncancerous stem cells. This is important not only for understanding the disease but also for designing strategies to limit the mortality it causes.

• Received for publication 4 September 2014.
• Accepted for publication 20 November 2014.

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