Applying statistical methods to a large dataset spanning almost 300 species, scientists found a positive correlation between body size and cancer prevalence [1]. Other researchers dispute that these findings invalidate the famous paradox.
A paradox of size
Cancer has forever been a mortal enemy of multicellular life. Sometimes, the cell’s “program” malfunctions, causing it to divide uncontrollably, until its progeny takes over the organism and kills it. This can happen to almost any cell, and one cell is enough.
A logical conclusion is that the more cells an animal has, the greater its risk of developing cancer. Hence, larger animals with many times more cells should be getting cancer much more frequently, but this does not appear to occur in nature. Instead, lifespan is positively correlated with body size (barring a few outliers), and small animals often get more cancer, not less. For instance, cancer is a highly prevalent cause of death in lab mice.
This became known as Peto’s paradox, after Sir Richard Peto, a British epidemiologist and statistician, who first articulated the idea in 1977 while studying cancer risks in different species. Of course, there’s nothing mystical about it: many large, long-lived species have developed superior anti-cancer defenses, such as DNA repair mechanisms, robust immune systems, and enhanced methods of removing cancerous cells through apoptosis. A lower cell division rate in some large species might also explain a part of the paradox.
For example, elephants have at least 20 copies of the TP53 gene, which plays crucial roles in detecting and repairing DNA damage and in triggering cell death in potentially cancerous cells, while humans have just one. Studying those mechanisms is a rapidly growing field in geroscience.
The correlation between body size and cancer
Since Peto’s original observation, several studies have investigated this question. Some of them found no correlation between cancer prevalence and body sizes, seemingly confirming the paradox [2]. However, those earlier studies were plagued by low data availability; after all, it’s hard to amass enough necropsies for multiple species.
Enter this new paper by scientists from the University of Reading, University College London and the Johns Hopkins University School of Medicine. This paper was published in Proceedings of the National Academy of Sciences (PNAS) and ambitiously titled “No evidence for Peto’s paradox in terrestrial vertebrates.”
The paper is based on a dataset created for a slightly earlier study by Compton et al. [3] The unprecedentedly large dataset consists of 16,049 necropsy records for 292 species, which made better statistical analysis possible. Interestingly, that paper did not reach the same definitive conclusion but instead highlighted “limitations to Peto’s paradox, by showing that large animals do tend to get somewhat more neoplasms and malignancies when compared with smaller animals.”
The authors of the PNAS paper claim to have applied more robust statistical analysis to the same dataset, which allowed them to extract a clearer signal. Professor Chris Venditti, senior author of the research at the University of Reading, said, “Everyone knows the myth that elephants are afraid of mice, but when it comes to cancer risk, mice are the ones who have less to fear. 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.”
The researchers separately analyzed birds and mammals, which stop growing at certain points in their life, along with amphibians and reptiles, many of which never do. In the first subset, the authors controlled for body mass, while in the second, for body length (which itself might have affected the results).
They found a significant positive association between neoplasia (this included both benign and malignant tumors, which were strongly correlated) and body size. For mammals, the relationship was β = 0.129, indicating a relatively flat slope (a linear relationship would have β = 1). In amphibians and reptiles, the correlation was stronger: β = 0.433. “Across all four vertebrate classes, larger species have an increased prevalence of malignancy compared to smaller species, thus demonstrating no evidence of Peto’s paradox,” the paper concludes.
The paradox is dead, long live the paradox
However, this suggests a narrow reading of Peto’s paradox as nothing short of zero positive correlation between cancer and body size. “The conclusion of this paper is not supported by the results,” said Dr. Vera Gorbunova of the university of Rochester, a researcher of long-lived species who was not involved in this study. “Even if there is a small statistical trend towards increased cancer with increased body size, it is not proportional to the number of cells or cell divisions experienced by larger species. An elephant still has much lower cancer incidence than a mouse. The authors themselves conclude that larger species have evolved better control of the cell cycle. This means they did evolve additional anticancer defenses, which is what Peto’s paradox posits.”
Indeed, the authors point to some instances of animals clearly “outsmarting” cancer, with elephants having 56% lower cancer rates than expected for their body size, and naked mole rats, rodents famous for their longevity, performing even stronger. On the opposite side of the spectrum lie the notoriously cancer-prone ferrets and opossums. Interestingly, bats and turtles, highlighted in Compton et al. as supporting Peto’s paradox, are not mentioned in this new study.
Dr. Joanna Baker, co-author from the University of Reading, said, “When species needed to grow larger, they also evolved remarkable defenses against cancer. 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.”
An important aspect of this study is that the researchers were able to count in some evolutionary differences. In particular, they found that species that evolved larger body sizes more rapidly, such as through a series of evolutionary ‘bursts’, were more likely to have stronger anti-cancer defenses.
“These studies represent a more comprehensive quantitative evaluation of some of the theories of evolution of aging and life history strategies,” said Dr. Emma Teeling of the University College Dublin, who also was not involved in this study. “Collecting these malignancy and life history studies requires decades if not centuries for long-lived species. This is why these studies are confined to captive species, where perhaps what was measured is actually the potential stress of captivity rather than true rate of malignancy. We are limited to species that we are able to maintain in captivity, which are not necessarily those that have evolved the most robust and therefore the most interesting anti-cancer mechanisms.”
“The authors detected a signal of evolution in action, where indeed with increased body size, there is a trend towards increased cancer incidence that then gets compensated by evolution of additional tumor suppressor mechanisms,” Gorbunova said. “Overall, I think the title of the paper is somewhat ‘sensationalized’. If this study found that upon certain phylogenetic comparisons larger species have slightly increased cancer risk, it does not eliminate Peto’s paradox.”
“The outliers in both of these studies, the species that were observed to have more or less than predicted cancer regardless of the methods used, are the most interesting candidates,” Teeling added. “Some of these species have been the focus of previous anti-aging research, such as the naked mole rat. Both studies will stimulate new ways to consider the evolution of cancer and anti-cancer mechanisms across the tree of life, new methods, datasets, and conclusions.”
Literature
[1] Butler, G., Baker, J., Amend, S. R., Pienta, K. J., & Venditti, C. (2025). No evidence for Peto’s paradox in terrestrial vertebrates. Proceedings of the National Academy of Sciences, 122(9), e2422861122.
[2] Boddy, A. M., Abegglen, L. M., Pessier, A. P., Aktipis, A., Schiffman, J. D., Maley, C. C., & Witte, C. (2020). Lifetime cancer prevalence and life history traits in mammals. Evolution, medicine, and public health, 2020(1), 187-195.
[3] Compton, Z. T., Mellon, W., Harris, V. K., Rupp, S., Mallo, D., Kapsetaki, S. E., … & Boddy, A. M. (2025). Cancer prevalence across vertebrates. Cancer discovery, 15(1), 227-244.
