No evidence for Peto’s paradox in terrestrial vertebrates

Abstract

Larger, longer-lived species are expected to have a higher cancer prevalence compared to smaller, shorter-lived species owing to the greater number of cell divisions that occur during their lifespan. Yet, to date, no evidence has been found to support this expectation, and no association has been found between cancer prevalence and body size across species—a phenomenon known as Peto’s paradox. Specifically, while anticancer mechanisms have been identified for individual species, wider phylogenetic evidence has remained elusive. Here, we show that there is no evidence for Peto’s paradox across amphibians, birds, mammals, and squamate reptiles: Larger species do in fact have a higher cancer prevalence compared to smaller species. Moreover, we demonstrate that the accumulation of repeated instances of accelerated body size evolution in mammals and birds is associated with a reduction in the prevalence of neoplasia and malignancy, suggesting that increased rates of body size evolution are associated with the evolution of improved cellular growth control. These results represent empirical evidence showing that larger body size is related to higher cancer prevalence, thus rejecting Peto’s paradox, and demonstrating the importance of heterogenous routes of body size evolution in shaping anticancer defenses.