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DNA Replication Errors Now Accepted as Cause of Substantial Number of Cancer Cases
Most textbooks attribute cancer-causing mutations to two major sources:
inherited and environmental factors. A recent study highlighted the
prominent role in cancer of replicative (R) mutations that arise from a
third source: unavoidable errors associated with DNA replication.
Tomasetti et al.
developed a method for determining the
proportions of cancer-causing mutations that result from inherited,
environmental, and replicative factors (see the Perspective by Nowak and
Waclaw). They found that a substantial fraction of cancer driver gene
mutations are indeed due to replicative factors. The results are
consistent with epidemiological estimates of the fraction of preventable
Cancers are caused by mutations that may be
inherited, induced by environmental factors, or result from DNA
replication errors (R). We studied the relationship between the number
of normal stem cell divisions and the risk of 17 cancer types in 69
countries throughout the world. The data revealed a strong correlation
(median = 0.80) between cancer incidence and normal stem cell divisions
in all countries, regardless of their environment. The major role of R
mutations in cancer etiology was supported by an independent approach,
based solely on cancer genome sequencing and epidemiological data, which
suggested that R mutations are responsible for two-thirds of the
mutations in human cancers. All of these results are consistent with
epidemiological estimates of the fraction of cancers that can be
prevented by changes in the environment. Moreover, they accentuate the
importance of early detection and intervention to reduce deaths from the
many cancers arising from unavoidable R mutationshttp://science.sciencemag.org/content/355/6331/1330