1999/07/01 by Cristian Tomasetti, Bert Vogelstein, 津太子 森 · 1 voice · 5 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #BRCA gene mutations in cancer #Cancer Cells and Metastasis #Cancer Genomics and Diagnostics #Genetic factors in colorectal cancer
paper · doi:10.1126/science.1260825
openalex publication_date 1999/07/01 · openalex created_date 2016/06/24 · openalex updated_date 2026/08/01
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.