A Test of the Adaptive Lag Hypothesis of the Evolution of Cancer Suppression and Lifespan in Dog Breeds

Background/Objectives: The well-established inverse relationship between lifespan and weight across dog breeds is associated with higher cancer mortality in larger breeds. However, Peto’s Paradox implies that larger-bodied species experience lower than expected cancer mortality because of higher levels of cancer suppression. Therefore, it has been hypothesised that recently established large dog breeds experience high cancer mortality because of a lag in their evolution of cancer suppression. This “adaptive lag hypothesis” predicts that ancient breeds, which have had more time to evolve optimal cancer suppression, exhibit lower cancer mortality rates, longer lifespans, and smaller litter sizes (a cost of cancer suppression) compared to modern breeds of the same size. Methods: The adaptive lag hypothesis is tested here by comparing ancient and modern breeds defined by their levels of modern European genetic admixture. Results: Ancient breeds have significantly longer lifespans and smaller litters than modern breeds of the same size after controlling for phylogenetic relationships. The sparse data on cancer mortality rates of ancient breeds do not allow a definitive test of a difference between ancient and modern breeds, but ancient breeds show a significant departure from the increase in cancer mortality rate with weight observed for modern breeds. Conclusions: The results are consistent with the adaptive lag hypothesis, that the evolution of cancer suppression in large modern dog breeds has lagged behind their increased risk of cancer, thus shortening their lives compared to smaller breeds and compared to ancient breeds of the same size.