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Large-scale mammal cancer study upholds decadeslong paradox

Cancers arise from mutations in cellular DNA, so it stands to reason species with more cells — or with longer lifespans and more cell divisions — should have higher cancer rates.

A new  study in the journal Nature shows that relationship doesn't hold up in nature. The key lay in looking beyond the two species scientists have the most cancer data about: humans and dogs. 

"It's clear there's a lot more to learn. This is just the first attempt to measure cancer rates across species. And going from two species where we know cancer rates to hundreds was a big step for us. But it's only really the beginning," said co-author and ASU evolutionary biologist Carlo Maley.

If size or age mattered most, mice would never get cancer, and whales would get it 1,000 times as often as humans. 

But this study pokes holes in that pattern and adds new evidence to Peto's Paradox, the 1977 observation by epidemiologist Richard Peto that body size does not correlate to cancer risk.

It's counterintuitive; yet, from a natural selection perspective, it also makes perfect sense. In the animal kingdom, size can be a boon, which is why large animals have repeatedly evolved on Earth. But advantages in areas like metabolism or resisting predation mean nothing if a species dies of cancer before it can procreate.

"You've got to be able to prevent cancer to get that large and live long enough to reproduce. So there's just a strong natural selective pressure to evolve ways of preventing cancer in these large, long lived organisms," said Maley, who is also director of the Arizona Cancer Evolution Center.

Although Peto's Paradox has long intrigued evolutionary biologists, a lack of cancer data in animals made it difficult to study. 

"There's discoveries to be made — that got us very excited years ago. But when you start asking the question, 'Well, what species are resistant to cancer? What are the cancer rates in different species?' What you quickly find out is, we don't know."

So Maley and his colleagues turned to a database of electronic medical records covering more than 100,000 zoo animals. Beyond providing further evidence for Peto's Paradox, a few clear patterns emerged from the data.

"Carnivores get a lot more cancer than animals that have other diets. And the next question, of course, is why. And that's still an open question." 

That's especially true among carnivores that munch on mammals. 

What's more, mammals also develop cancer more often than amphibians, reptiles or birds.

Researchers suspect evolved biological resistances — or exposures to carcinogenic toxins and viruses — tip the scales one way or the other. Environmental toxins can became concentrated as they move up the food chain, and carnivores that consume raw meat might be exposed to more pathogens.

Such answers await further study. 

"There's a larger question about how to understand cancer, because the way we've understood it and defined it is all very much from a human-centric point of view. So one thing we're trying to do is get a deeper fundamental understanding of cancer by seeing how it shows up in other species," said Maley. 

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Nicholas Gerbis was a senior field correspondent for KJZZ from 2016 to 2024.