Cancer prevalence is related to body mass and lifespan in tetrapods and remarkably low in turtles

Abstract

Cancer rates vary widely across vertebrate groups. Identifying species with lower-than-expected cancer prevalence can help establish new models for unraveling the biological mechanisms underlying cancer resistance. Theoretical predictions suggest that cancer prevalence should be positively associated with body mass and longevity in animals. Yet, in mammals, the best studied vertebrates in terms of cancer, this prediction does not hold true - a phenomenon known as Peto's paradox. Despite mounting work disentangling the biological basis of Peto's paradox, it is still relatively unknown whether other major vertebrate groups behave similarly to mammals or might hold new keys to understanding cancer biology. Here, we present the largest dataset available so far on cancer prevalence across all major groups of tetrapod vertebrates: amphibians, birds, crocodilians, mammals, squamates (lizards and snakes), and turtles. We investigated cancer prevalence within and among these groups and its relationship with body mass and lifespan. This is the first study to analyze non-avian reptile groups separately. We found remarkably low cancer prevalence in birds, crocodilians, and turtles. Counter to previous studies, we found that body mass and lifespan are inversely related to cancer prevalence in mammals, although Peto's paradox still holds true in this group. Conversely, we rejected Peto's paradox in birds and squamates, as neoplasia prevalence was positively associated with body mass in these groups. The exceptionally low cancer prevalence in turtles and extensive variation in cancer prevalence amongst vertebrate families hold particular promise for identifying species with novel mechanisms of cancer resistance.

Cancer Prevalence Across Vertebrates

“…We validated our results by implementing phylogenetic binomial regressions 19 on records that include the age of the animal. All the above statistically significant relationships are still significant at p < 0.05 level using binomial regressions.…”

“…pglsSEyPagel expands upon the pglsSEy function by adding the estimate of Pagel's lambda 65 to the regression, rather than assuming it is fixed at 1 (i.e., Brownian motion). Compar.gee is another method from the "ape" package that utilizes phylogenetic input, but uses a Generalized Estimating Equation to carry out binomial regressions 19 which take into account the sample size for each species. The p-values for malignancy and neoplasia prevalence varied minimally when univariate tests for body mass, longevity, and gestation length were conducted.…”

Parallel evolution of reduced cancer risk and tumor suppressor duplications in Xenarthra

“…This risk is compounded by a general positive correlation between body size and lifespan across vertebrates ( Caulin et al, 2015 ; Caulin and Maley, 2011 ; Nagy et al, 2007 ; Peto, 2015 ). While this strong positive correlation between body size, age, and cancer prevalence holds within species ( Dobson, 2013 ; Green et al, 2011 ; Nunney, 2018 ), between mammalian species there is no correlation between either body size or lifespan and cancer risk ( Abegglen et al, 2015 ; Boddy et al, 2020 ; Bulls et al, 2022 ; Vincze et al, 2022 ). This lack of correlation is often referred to as ‘Peto’s Paradox’ ( Peto, 2015 ).…”

Parallel evolution of reduced cancer risk and tumor suppressor duplications in Xenarthra

“…If similar cell-types in large and small animals, for example, have a similar risk of malignant transformation and equivalent cancer suppression mechanisms, large organism with many cells should have a higher risk of developing cancer than small organisms with fewer cells; Similarly the cells of organisms with long lifespans have more time to accumulate cancer-causing mutations and other types of damage than organisms with shorter lifespans and therefore should be at an increased risk of developing cancer, a risk that is compounded in large bodied, long-lived organisms (Caulin et al, 2015; Caulin and Maley, 2011; Nagy et al, 2007; Peto, 2015). While there is a strong positive correlation between body size, age, and cancer prevalence within species (Dobson, 2013; Green et al, 2011; Nunney, 2018), there are no correlations between body size and cancer risk or lifespan and cancer risk between mammalian species (Abegglen et al, 2015; Boddy et al, 2020; Bulls et al, 2022; Vincze et al, 2022) – this lack of correlation is often referred to as ‘Peto’s Paradox’ (Peto, 2015).…”