Peto's paradox and the promise of comparative oncology

Abstract

One contribution of 18 to a theme issue 'Cancer across life: Peto's paradox and the promise of comparative oncology'.Subject Areas: evolution, health and disease and epidemiology, molecular biology, physiology Keywords:Peto's paradox, comparative oncology, evolution, life-history theory, cancer, modelling The past several decades have seen a paradigm shift with the integration of evolutionary thinking into studying cancer. The evolutionary lens is most commonly employed in understanding cancer emergence, tumour growth and metastasis, but there is an increasing realization that cancer defences both between tissues within the individual and between species have been influenced by natural selection. This special issue focuses on discoveries of these deeper evolutionary phenomena in the emerging area of 'comparative oncology'. Comparing cancer dynamics in different tissues or species can lead to insights into how biology and ecology have led to differences in carcinogenesis, and the diversity, incidence and lethality of cancers. In this introduction to the special issue, we review the history of the field and outline how the contributions use empirical, comparative and theoretical approaches to address the processes and patterns associated with 'Peto's paradox', the lack of a statistical relationship of cancer incidence with body size and longevity. This burgeoning area of research can help us understand that cancer is not only a disease but is also a driving force in biological systems and species life histories. Comparative oncology will be key to understanding globally important health issues, including cancer epidemiology, prevention and improved therapies.

Telomere length is highly heritable and independent of growth rate manipulated by temperature in field crickets

“…Recent syntheses propose that telomere length of vertebrates may be under stabilizing selection by functioning as an anti-cancer mechanism (Aviv et al 2017;Young 2018). This hypothesis is primarily based on the observation that larger vertebrates with long periods of growth tend to have shorter telomeres than small vertebrates and the premise that this relationship coexists with a higher cancer risk in larger species, but see (Nunney et al 2015). Shorter telomere length could be adaptive in large vertebrates when it selectively shuts down cell proliferation of unstable cells.…”

Mutations, Cancer and the Telomere Length Paradox

“…Given that replications of somatic cells increase the organismal mutation burden and hence cancer risk, Peto reasoned four decades ago that large mammals should have more cancer than small ones, yet there is no evidence that cancer risk scales with body size [17]. Large mammals, who are by and large long-living [18], have developed an array of anti-cancer defenses, a few of which might be unique for a given species, while others are shared across species.…”

Turning natural adaptations to oncogenic factors into an ally in the war against cancer

“…Indeed, if every cell has some chance of becoming cancerous, large long‐lived organisms should have an increased risk of developing cancer compared to small, short‐lived organisms. The lack of correlation therewith suggests that the mechanisms of cancer resistance must have been more strongly selected in large and long‐lived species (Caulin & Maley, ; Nunney, Maley, Breen, Hochberg, & Schiffman, ; Roche et al., ). Accordingly, it has for instance been shown that large vertebrates such as elephants have 20 copies of TP53 (humans have only one), horses seem to have larger number of T‐cell differentiation protein (MAL) genes, and bats (that live unexpectedly long given their small body size) have amplified F‐box protein 31 (FBXO31) (Caulin, Graham, Wang, & Maley, ; Harris, Schiffman, & Boddy, ; Kokko, Schindler, & Sprouffske, ).…”