Paradox-Busting Study Finds Bigger Animals Really Are at Greater Risk of Cancer

Despite decades of research, scientists were still trying to figure out why rates of malignant cancer do not appear to increase with an animal species' size – a paradox first proposed in 1977 by Richard Peto.

A new study may have just put the paradox to rest, finding larger species like giraffes and pythons do have higher cancer rates than smaller ones like bats and frogs after all.

The results did find a curious link between repeated jumps in body size in a species' history and a reduction in tumors and malignancies.

Cancer is typically caused by gene mutations in cells leading to uncontrolled cell division. It would make sense for animals with more cells to have a greater chance of a cancer-causing mutation. Since larger animals tend to have longer lifespans, that risk should grow with time. Yet studies kept failing to find this.

University College London computational biologist George Butler and colleagues suspect this trend was missed for so long because not enough samples of each species were drawn on in the studies probing it, which also relied on methods that biased results, confounding the high level of variation between individuals in a species.

Using a different statistical approach that avoided this bias, Butler and team found the long-elusive but expected trend in terrestrial animals by examining 263 species of amphibians, birds, mammals, and reptiles, and pooling their cancer prevalence data before analyzing it.

"We've shown that larger species like elephants do face higher cancer rates – exactly what you'd expect given they have so many more cells that could go wrong," explains University of Reading evolutionary biologist Chris Venditti.

Some species, however, do buck this trend. The budgerigar (Melopsittacus undulatus) has more than 40 times the rate of cancer that would be expected for an animal weighing less than 30 grams.

Other animals, like elephants, that rapidly evolved into their large sizes, also have a lower cancer rate than expected for their size. Their rate of developing malignant tumors is on par with animals one-tenth of their size, such as tigers.

"When species needed to grow larger, they also evolved remarkable defenses against cancer," explains University of Reading evolutionary biologist Joanna Baker.

"Elephants shouldn't fear their size – they developed sophisticated biological tools to keep cancer in check. It's a beautiful example of how evolution finds solutions to complex challenges."

This suggests adaptations in managing cell growth may coincide with pressures that increase the rate at which an animal increases in size.

These defenses could provide insights into treating this insidious disease.

"Finding which animals are naturally better at fighting off cancer opens exciting new paths for research," says Butler.

"By studying these successful species, we can better understand how cancers develop and potentially discover new ways to fight the disease. This could lead to breakthrough treatments in the future."

This research was published in PNAS.