Paradox resolved: The allometric scaling of cancer risk across species

Abstract: Understanding the cross-species behavior of cancer is important for uncovering fundamental mechanisms of carcinogenesis, and for translating results of model systems between species. One of the most famous interspecific considerations of cancer is Peto's paradox, which asserts that organisms with vastly different body mass are expected to have a vastly different degree of cancer risk, a pattern that is not observed empirically. Here we show that this observation is not a paradox at all but follows naturally from the interspecific scaling of metabolic rates across mammalian body size. We connect metabolic allometry to evolutionary models of cancer development in tissues to show that waiting time to cancer scales with body mass in a similar way as normal organism lifespan does. Thus, the expectation across mammals is that lifetime cancer risk is invariant with body mass. Peto's observation is therefore not a paradox, but the natural expectation from interspecific scaling of metabolism and physiology. These allometric patterns have theoretical implications for understanding life span evolution, and practical implications for using smaller animals as model systems for human cancer.