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

      Science (New York, N.Y.)
      Cell Division, genetics, Gene-Environment Interaction, Genetic Variation, Humans, Mutation, Neoplasms, classification, epidemiology, Risk, Stem Cells, physiology

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          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. Copyright © 2015, American Association for the Advancement of Science.

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          Author and article information

          Journal
          25554788
          4446723
          10.1126/science.1260825

          Chemistry
          Cell Division,genetics,Gene-Environment Interaction,Genetic Variation,Humans,Mutation,Neoplasms,classification,epidemiology,Risk,Stem Cells,physiology

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