Reacción a "Study shows that larger species do develop more cases of cancer, disproving Peto's paradox"

What do you think of the study overall? Is it of good quality? 

“This study provides an interesting analysis of the relationship between body size and cancer prevalence. The authors use advanced phylogenetic comparative methods, and the diversity of species analyzed (amphibians, birds, mammals, and reptiles) offers a broad and relevant framework. However, it is important to note that the entire message of this PNAS paper relies on specific statistical choices, which remain just that—choices. These choices, as in any complex analysis, are more or less debatable. In this context, there is no doubt that other scientists may legitimately take a critical perspective on this work and its conclusions”. 

How does it fit with the existing evidence, and what is new about it? What implications could it have? 

“This study revisits a fundamental question in evolutionary biology and comparative oncology: the relationship between body size and cancer prevalence. Unlike some previous research that found no systematic link, it highlights a positive association between size and malignancy across the four vertebrate classes studied.  

It also suggests that, in birds and mammals, rapid evolutionary increases in body size are associated with a decreased prevalence of cancer, implying the co-evolution of enhanced cellular growth control mechanisms. However, within the philosophy of Peto’s paradox, the real question is not just whether there is a positive relationship between size and cancer prevalence, but whether this relationship is as strong as expected given the increased number of cell divisions associated with larger body size. In other words, there may be a positive correlation between size and cancer risk, but if this correlation is weaker than statistically expected, it suggests that natural selection has nonetheless favored superior anti-cancer defenses in large-bodied species. This is a crucial point, as it highlights the evolutionary trade-offs between growth, longevity, and disease resistance”. 

Are there important limitations to take into account? 

“Like any macro-evolutionary study, it relies on cancer prevalence data that may be incomplete or heterogeneous across species. Moreover, the precise mechanisms underlying anti-cancer adaptations remain to be explored in more detail, particularly through functional or molecular approaches. Another potential limitation is the influence of biases related to lifespan and alternative causes of mortality, which may affect cancer prevalence estimates. Furthermore, given that the study’s conclusions rest on specific statistical decisions, it is essential to consider how different methodological approaches might lead to alternative interpretations. This reinforces the need for a cautious reading of the results and for future studies to explore different modeling strategies to assess the robustness of these findings. 

Beyond size and longevity, other factors should be considered. Our team has also proposed that, to understand the evolution of anti-cancer defenses, it is essential to broaden the focus to other traits that, in theory, should increase cancer risk but where evolutionary compensation may exist. For example, pronounced secondary sexual traits (such as antlers in deer) involve rapid and repeated cell growth, which could promote tumor formation. However, these species do not systematically exhibit high cancer rates, suggesting the presence of specific adaptations to mitigate this risk. Similarly, structures like invasive placentas, which induce intense cellular proliferation, could be associated with reinforced tumor control mechanisms. This integrative approach would provide a more comprehensive view of the anti-cancer strategies that have evolved over time”.