Is creeping abandonment of human cancer defences evolutionarily favoured?

Abstract

Among observed animal species, humans exhibit a remarkably elevated lifetime cancer risk (over 38%), in stark contrast to less than 10% seen in other observed species (excluding those affected by environmental pollution). Peto's paradox suggests that these observations defy explanation through mathematical models treating cancer genesis as a stochastic process, with risks resulting from lifespan and body mass. For instance, whales, despite longer lifespans and roughly 30 times the size of humans, maintain consistent cancer risk throughout life, differing from the pronounced increase after female reproductive age observed in humans. It is well-documented in the literature that species-specific tumor suppression mechanisms allow for large lifespan and body mass. Examination of data from chimpanzees, a closely related species, suggests—without definitive evidence—a major difference between chimpanzee and human cancer risk. This leads to the conjecture that vulnerability of cancer defence mechanisms in humans might have emerged due to the unique evolutionary trajectory of the genus _Homo_. Given that this vulnerability emerges after reproductive years, a prevailing hypothesis attributes it to antagonistic pleiotropy. However, considering _Homo's_ historical existence in small tribes throughout much of evolution, we suggest that natural selection may have also operated at the tribal level. Consequently, our hypothesis, "Is creeping abandonment of human cancer defences evolutionarily favored?" arises from two alternative speculative scenarios. One proposition rests on the notion that diminishing tumor suppression activities could confer a calorie-saving advantage, particularly beneficial for tribes with limited food resources. The other proposition suggests that creeping abandonment of cancer defences might promote genetic diversity.