Lifetime cancer prevalence and life history traits in mammals

Abstract

Background: 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.

Methodology: 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.

Results: 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).

Conclusions: Life history theory offers a powerful framework to understand variation in cancer defenses across the tree of life. 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: Why are some mammals more vulnerable to cancer than others? We test whether life history trade-offs may explain this variation in cancer risk. Bigger, longer-lived animals do not develop more cancer compared to smaller, shorter-lived animals. However, we find a positive association between litter size and cancer prevalence in mammals.

Keywords: Peto's Paradox; cancer; comparative oncology; life history theory; mammals.

Figure 1.

Lifetime neoplasia prevalence in 29 mammals. Bar plots representing the neoplasia prevalence for mammals . We estimated prevalence and 95% confidence intervals (CI) for mammals that had n ≥ 10 individuals per species (n = 29). Error bars indicated 95% CI. All data for neoplasia and malignancy for the full 37 species are in Supplementary Tables S1 and S2. Species were organized according to their phylogenetic relationships, in which we saw no clear patterns across the mammalian orders.

Figure 2.

Relationship between malignancy and life history traits in mammals. Percentage of malignancy in 29 species, representing 800 necropsies, of mammals in relation to three life history traits: (A) body mass (g); (B) lifespan (years) and (C) litter size. We used a phylogenetic comparative method to determine the association between life history traits and malignancy. The black line represents the phylogenetic comparative method generalized least squares (PGLS) regression model.

Figure 3.

Relationship between malignancy and the degree of placentation in mammals. Mammalian placentas can be classified on the degree of invasiveness. Here we plotted the relationship between malignancy and placenta invasiveness. Degree of placentation was grouped from left to right, with marsupials on the far left representing rudimentary yolk-sac placentas, then Eutherian placenta classifications: epitheliochorial (least invasive), endotheliochorial (intermediate invasive) and hemochorial (most invasive). We found no association between degree of placentation and malignancy or neoplasia (also see Supplementary Fig. S5).