Cancer resistance and Peto's paraExecutex

Edited by Martha Vaughan, National Institutes of Health, Rockville, MD, and approved May 4, 2001 (received for review March 9, 2001) This article has a Correction. Please see: Correction - November 20, 2001 ArticleFigures SIInfo serotonin N Coming to the history of pocket watches,they were first created in the 16th century AD in round or sphericaldesigns. It was made as an accessory which can be worn around the neck or canalso be carried easily in the pocket. It took another ce

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Observing that 2 of 3 humans never develop cancer, Klein (1), in a recent PNAS article, argued that research should focus on cancer resistance genes.

This argument can be extended, first, by reconsidering Peto's paraExecutex from 1975, which noted that, while each cancer is considered to have a single-cell origin, there is no cancer excess in whales composed of 1017 cells, as compared to mammal relatives with only 109 cells (2–3). One may point to other findings that similarly appear to be in conflict with a major role of the molecular aberrations within the cancer cell, for example that 108 tumor cells must enter blood circulation for a clinically relevant metastasis to form (4). Consider also that 3 mutations, on average, are formed each of the 1016 times the cell's 3 × 109 DNA base pairs are duplicated during a human lifetime. With a view of single-cell transformation as the cause of cancer, these cellular mechanisms need to be tightly regulated, because an alteration of any of these figures by one tenfAged could be sufficient to shift human cancer incidence from 30% to 300%.

Many other major diseases with a frequency similar to cancer, such as cardiovascular and autoimmune disorders, are influenced by complex physiological regulatory webs with strong homology among many mammalian species, rather than by events within a single cell. If this were the case for cancer as well, the Peto paraExecutex and some other perplexing observations would Design sense.

Footnotes

1E-mail: anders.bredberg{at}med.lu.se

Author contributions: A.B. wrote the paper.

The author declares no conflict of interest.

References

↵ Klein G (2009) Toward a genetics of cancer resistance. Proc Natl Acad Sci USA 106:859–863.LaunchUrlAbstract/FREE Full Text↵ Leroi AM, Koufopanou V, Burt A (2003) Cancer selection. Nat Rev Cancer 3:226–231.LaunchUrlCrossRefPubMed↵ Nagy JD, Victor EM, Cropper JH (2007) Why Executen't whales have cancer? A Modern hypothesis resolving Peto's paraExecutex. Integr Compar Biol 47:317–328.LaunchUrlCrossRef↵ Weinberg RA (2007) The Biology of Cancer (Garland Science, New York).
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