Lifetime cancer prevalence and life history traits in mammals

Abstract

Cancer is a common diagnosis in many mammalian species, yet they vary in their vulnerability to cancer. The factors driving this variation are unknown, but life history theory offers potential explanations to why cancer defense mechanisms are not equal across species. Here we report the prevalence of neoplasia and malignancy in 37 mammalian species, representing 11 mammalian orders, using 42 years of well curated necropsy data from the San Diego Zoo and San Diego Zoo Safari Park. We collected data on life history components of these species and tested for associations between life history traits and both neoplasia and malignancy, while controlling for phylogenetic history. These results support Peto’s paradox, in that we find no association between lifespan and/or body mass and the prevalence of neoplasia or malignancy. However, a positive relationship exists between litter size and prevalence of malignancy (p=0.005, Adj. R2=0.212), suggesting that a species’ life history strategy may influence cancer vulnerabilities. Lastly, we tested for the relationship between placental invasiveness and malignancy. We find no evidence for an association between placental depth and malignancy prevalence (p=0.618, Adj. R2=0.068). These findings provide insight into the relationship between life history traits and cancer vulnerabilities, which suggest a trade-off between reproduction and cancer defenses. Lay Summary Comparative oncology

Pervasive duplication of tumor suppressors in Afrotherians during the evolution of large bodies and reduced cancer risk

“…In order to account for a relatively stable cancer rate across species [10][11][12], intrinsic cancer risk must also evolve with changes body size (and lifespan) across species. As expected, intrinsic cancer risk in Afrotheria also varies with changes in body size and longevity ( Fig.…”

“…Indeed, cancer prevalence is relatively stable at ~5% across species with diverse body sizes ranging from the minuscule 51g grass mouse to the gargantuan 4800kg African elephant [10][11][12].…”

On the comparative biology of mammalian telomeres: Telomere length co-evolves with body mass, lifespan and cancer risk

“…We compiled neoplasia incidence rates in 7 species of mammals from a medically curated postmortem database published by Boddy et al (2020) in addition to 15 species from various sources in the literature reviewed by Albuquerque et al (2018) and shown in Table S10. In all studies, the number of individuals with abnormal growth including both benign and malignant tumors (neoplasia) out of the total number of necropsies were used to define the neoplasia prevalence rate (%).…”

“…For the large treeshrew (Tupaia tana ) neoplasia rate is unknown, so we used the estimate reported for the closely related common treeshrew (Tupaia glis ). Due to small samples sizes, neoplasia data were combined in Boddy et al (2020) for the Asian and African elephant (Elephas maximus and Loxodonta africana ), so we used the average TL, mass and lifespan of the two species, which are similar (Table S9), in subsequent analyses. Boddy et al (2020) also provided estimates of lifetime prevalence of malignant neoplasms (invading surrounding normal tissue) of 29 mammal species, allowing us to test if neoplasia prevalence is generally a good predictor of malignancy prevalence (i.e.…”

“…Telomere biology is widely assumed to influence cancer risk and thus for different species to evolve different telomere dynamics in response to differing fitness costs of cancer. Cancer occurs in almost all vertebrates, but among wild animals, cancer incidence rates are little studied, but seem to vary considerably (Effron et al 1977;Pesavento et al 2018;Albuquerque et al 2018;Boddy et al 2020). For instance, cancer is rarely reported in long-lived whales, bats or naked mole-rats, while rats and mice are known to be much more prone to cancer (Albuquerque et al 2018).…”