Fine-tuning of cancer incidence across species: rethinking cancer from an evolutionary and ecological perspective

CATALINA SIERRA; JULIÁN MAXWELL; NICOLÁS FLAIBANI; CONSTANZA SÁNCHEZ DE LA VEGA; ALEJANDRA VENTURA; NICOLÁS LAVAGNINO; MATÍAS BLAUSTEIN

Congreso; 7th International Congress on Logic, Methodology and Philosophy of Science and Technology; 2023

Cancer is associated with the accumulation of mutations throughout the life of a multicellular organism. Therefore, the probability of developing cancer increases as an individual gets older. Since cancer negatively impacts survival of individuals, classic evolutionary explanations have had to account for the prevalence of cancer across the tree of life. Cancer-promoting gene variants have been traditionally associated with either negative or neutral fitness value. In the first case, these variants are proposed to be related to other phenotypic traits on which positive selection operates (antagonistic pleiotropy). Alternatively, they are conceived as neutral traits since cancer tends to occur after reproduction. However, some mammals present molecular mechanisms that confer strong or even full resistance to developing tumors, confirming that multicellularity can evolve without cancer as an inevitable by-product. On the other hand, the existence of other mammalian species with high incidence of malignant tumors suggests that cancer may also be acting as a phenoptosis mechanism (programmed organism death) on less reproductive adults. In fact, ecological systems can experience counterintuitive increases in population size (what is known as the hydra paradox) or stability, when a subpopulation exhibits higher mortality rates. Here, we present the hypothesis that cancer mortality rates across the tree of life might have been fine-tuned by evolution. A high incidence of cancer could have a neutral, negative or even positive adaptive value, depending on the evolutionary history, environment and context of each species. By using public databases on cancer-related mortality of adult zoo mammals (110.148 individuals, 191 species), we show that species with higher intraspecific competence (solitary animals, large litter size) display higher cancer mortality rates; while species with cooperative and caring habits (group living, small litter size) have lower cancer mortality rates. We validated these results by using two paradigmatic external groups of wild animals with either high tumor incidence or strong resistance to cancer. Finally, we demonstrate by mathematical modeling that higher mortality rates in older less reproductive individuals can lead to an increase in the population size in a context of intraspecific competition (hydra effect). On the contrary, in a context of cooperation, population size increases as mortality rates of older and less reproductive individuals decrease. Our results approach the phenomenon of cancer from a multidimensional perspective and are compatible with a co-evolution of cancer incidence and other physiological, ecological, and behavioral aspects across the tree of life. Should this be the case, cancer incidence could be then considered as an exaptation, a trait that has been co-opted for distinct functions over the evolution course of multicellular organisms.