Question ID: WS-103
Submitted by: Aleah Caulin
June 29, 2011
What mechanisms have evolved in large, long-lived organisms, like elephants and whales, to suppress cancer and how can this be translated into improved cancer prevention in humans? Though this was briefly addressed in the question submitted by Dr. Rui Sousa, we think that this topic is important enough to warrant its own question. Peto’s paradox is the observation that lifetime cancer risk does not increase with body size and lifespan. We would expect that more cells accumulating mutations for a longer period of time would increase the risk of cancer for an organism, but this is not observed. How do large, long-lived organisms suppress cancer more effectively than humans?
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Comments
Submitted By James Sherley
Dear Dr. Caulin:
Please, consider the concept, previously developed by Cairns, Knudson, Thilly and others, that if asymmetrically self-renewing tissue stem cells are the major cell of tumor origin, then Peto's paradox is resolved. The lifetime cancer risk of different mammalian species will be related to their tissues' stem cell fraction and the mutation rate of the stem cells. In addition, Cairns proposed nonrandom template DNA strand inheritance (also known as immortal DNA strand co-segregation) as a mechanism by which tissue stem cells limit their rate of accumulation of carcinogenic mutations. Incorporation of these ideas into spontaneous cancer risk models leads to a different set of expectations for whether lifetime cancer risk should scale with species body size and lifespan. A longer-lived species with a low tissue stem cell fraction could have the same lifetime cancer risk as a shorter-lived species with a high tissue stem cell fraction, depending on their stem cell mutation rate.
James Sherley
Adult Stem Cell Technology Center
Boston Biomedical Research Institute
Watertown, MA
