title: Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions.
abstract: 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.
authors.affiliation: Division 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. ctomasetti@jhu.edu vogelbe@jhmi.edu.
authors.forename: Cristian
authors.initials: C
authors.lastname: Tomasetti
authors.affiliation: Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, 1650 Orleans Street, Baltimore, MD 21205, USA. ctomasetti@jhu.edu vogelbe@jhmi.edu.
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
mesh_terms: D002455:Cell Division / Q000235:genetics*; D059647:Gene-Environment Interaction; D014644:Genetic Variation; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000145:classification / Q000453:epidemiology* / Q000235:genetics*; D012306:Risk; D013234:Stem Cells / Q000502:physiology*