Sarver Aaron L, Makielski Kelly M, DePauw Taylor A, Schulte Ashley J, Modiano Jaime F
Masonic Cancer Center, University of Minnesota, Minneapolis, MN.
Institute for Health Informatics, University of Minnesota, Minneapolis, MN.
Aging Cancer. 2022 Mar;3(1):3-19. doi: 10.1002/aac2.12046. Epub 2022 Feb 23.
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 2-4 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.
在发达国家,癌症是导致犬类(和猫类)以及人类死亡的最常见原因之一,尽管在野生动物和其他家畜中并不常见。基于我们对癌症进化基础理解的最新进展,我们为这一观察结果提供了一个理论依据。在进化过程中,物种已经获得并微调了与它们的能量需求、繁殖策略和预期寿命内在相关的适应性癌症保护机制。这些癌症保护机制在物种间具有普遍性和/或特定于每个物种及其生态位,而且它们在多样性方面似乎没有限制。定义一个物种生命历程的进化获得的无癌长寿可以解释为什么尽管动物王国中大多数物种的体型和预期寿命存在差异,但它们的相对癌症风险、发生率和发病率在很大程度上是相似的。促进恶性转化和癌性生长的分子、细胞和代谢事件可以在一小部分个体中克服这些适应性的、物种特异性的保护机制,而独立地,种群中的一些个体可能实现超长寿命。在犬类和人类中,近期医疗保健和社会结构的巨大变化使得这两个物种中越来越多的个体远远超过了它们适应物种的寿命(达到2至4倍),却没有给予补偿性自然选择所需的时间。换句话说,在其适应的寿命期间将风险限制在与其他物种相当水平的癌症保护机制,无法在近期这种急剧且广泛的寿命延长情况下提供癌症保护。