Increased risk of cancer in dogs and humans: A consequence of recent extension of lifespan beyond evolutionarily determined limitations?. Issue 1 (23rd February 2022)

• Record Type: Journal Article
• Authors: Sarver, Aaron L.; Makielski, Kelly M.; DePauw, Taylor A.; Schulte, Ashley J.; Modiano, Jaime F.
• Is Part Of: Aging and cancer. Volume 3:Issue 1(2022)
• Page Start: 3
• Page End: 19
• Publication Date: 2022-02-23
• Subjects: cancer‐protective mechanisms -- cancer risk -- evolution -- longevity; Cancer -- Age factors -- Periodicals; Geriatric oncology -- Periodicals; Electronic journals; Periodicals; 616.994
• DOI: 10.1002/aac2.12046
• Languages: English
• ISSNs: 2643-8909

Abstract

Abstract: Cancer is among the most common causes of death for dogs (and cats) and humans in the developed world, even though it is uncommon in wildlife and other domestic animals. We provide a rationale for this observation based on recent advances in our understanding of the evolutionary basis of cancer. Over the course of evolutionary time, species have acquired and fine‐tuned adaptive cancer‐protective mechanisms that are intrinsically related to their energy demands, reproductive strategies, and expected lifespan. These cancer‐protective mechanisms are general across species and/or specific to each species and their niche, and they do not seem to be limited in diversity. The evolutionarily acquired cancer‐free longevity that defines a species' life history can explain why the relative cancer risk, rate, and incidence are largely similar across most species in the animal kingdom despite differences in body size and life expectancy. The molecular, cellular, and metabolic events that promote malignant transformation and cancerous growth can overcome these adaptive, species‐specific protective mechanisms in a small proportion of individuals, while independently, some individuals in the population might achieve exceptional longevity. In dogs and humans, recent dramatic alterations in healthcare and social structures have allowed increasing numbers of individuals in both species to far exceed their species‐adapted longevities (by two to four times) without allowing the time necessary for compensatory natural selection. In other words, the cancer‐protective mechanisms that restrain risk at comparable levels to other species for their adapted lifespan are incapable of providing cancer protection over this recent, drastic, and widespread increase in longevity. Abstract : Peto's paradox states that, at the species level, cancer incidence is not correlated with the number of cells in an organism. Furthering the paradox, cancer incidence is also not correlated with longevity among different species. One explanation for the relatively low cancer rates in large and/or long‐lived species, exemplified here by bowhead whales, African elephants, and African naked mole rats, is the evolution of tumor suppressive mechanisms, unique to each species, over millions of years. In contrast to these species, cancer is among the most common causes of death in modern dogs and in modern humans. Both of these species share a recent, dramatic increase in life expectancy driven by breakthroughs in medicine and technology, and without concurrent evolutionary adaptations that can protect individuals from cancer in the years of life "beyond what nature intended." Thus, a reasonable approach to address the apparent cancer epidemic would be to prevent the disease entirely. We are developing tests for early cancer detection and risk stratification in dogs, paired with targeted prophylaxis, with the goal of preventing or delaying the emergence of cancer. This proof‐of‐concept in dogs would set a path for development of comparable approaches in humans.