Publication Date:
2015-01-03
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4446723/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4446723/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tomasetti, Cristian -- Vogelstein, Bert -- P30 CA006973/CA/NCI NIH HHS/ -- P30-CA006973/CA/NCI NIH HHS/ -- P50-CA62924/CA/NCI NIH HHS/ -- R01-CA57345/CA/NCI NIH HHS/ -- R37 CA043460/CA/NCI NIH HHS/ -- R37-CA43460/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Jan 2;347(6217):78-81. doi: 10.1126/science.1260825.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉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. ; 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.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25554788" target="_blank"〉PubMed〈/a〉
Keywords:
Cell Division/*genetics
;
Gene-Environment Interaction
;
Genetic Variation
;
Humans
;
Mutation
;
Neoplasms/classification/*epidemiology/*genetics
;
Risk
;
Stem Cells/*physiology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
