Cancer Rates Consistent Across Species Instead of Increasing Due to Body Mass
Posted on October 12, 2015 Comments (1)
It would seem sensible to think cancer should be more prevalent in species with a huge number of cells, and thus more cells to become cancerous. But cancer risk doesn’t increase in this way. This interesting, open source paper, sheds some light on what is behind this.
Solutions to Peto’s paradox revealed by mathematical modelling and cross-species cancer gene analysis
Whales have 1000-fold more cells than humans and mice have 1000-fold fewer; however, cancer risk across species does not increase with the number of somatic cells and the lifespan of the organism. This observation is known as Peto’s paradox. How much would evolution have to change the parameters of somatic evolution in order to equalize the cancer risk between species that differ by orders of magnitude in size? Analysis of previously published models of colorectal cancer suggests that a two- to three-fold decrease in the mutation rate or stem cell division rate is enough to reduce a whale’s cancer risk to that of a human. Similarly, the addition of one to two required tumour-suppressor gene mutations would also be sufficient.
We surveyed mammalian genomes and did not find a positive correlation of tumour-suppressor genes with increasing body mass and longevity. However, we found evidence of the amplification of TP53 in elephants, MAL in horses and FBXO31 in microbats, which might explain Peto’s paradox in those species. Exploring parameters that evolution may have fine-tuned in large, long-lived organisms will help guide future experiments to reveal the underlying biology responsible for Peto’s paradox and guide cancer prevention in humans.
In another way it would make sense that large animals would have hugely increased risks of cancer. As they evolved, extremely high cancer rates would be a much bigger problem for them. Therefore it wouldn’t be surprising to find they have evolved a way of reducing cancer risks.
Despite these limitations, we found genes that have been dramatically amplified in specific mammalian genomes, the most interesting of which is the discovery of 12 TP53 copies in the genome of the African elephant. We subsequently cloned those genes and identified 19 distinct copies of TP53 in African elephants and 15–20 in Asian elephants . Another potential lead for solving Peto’s paradox is MAL, which is found to have eight copies in the horse genome and two in microbat. This could be an example of convergent evolution where a large animal (horse) and a small, long-lived animal (microbat) both evolved extra copies of the same gene to overcome their increased risk of cancer. Further analysis and experimentation would need to be performed to determine the function of these copies and whether or not they provide enhanced suppression of carcinogenesis.
The researchers have found an interesting potential explanation for how that has been accomplished.
Related: The Only Known Cancerless Animal (the naked mole rat) – Webcast of a T-cell Killing a Cancerous Cell – Researchers Find Switch That Allows Cancer Cells to Spread – Cancer Vaccines
Posted by curiouscat
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