Towards a more robust comparative oncology: a Bayesian reanalysis of Peto’s paradox and discussion of comparative cancer risk studies in vertebrates
The multistage carcinogenesis model predicts that cancer risk should increase with body size and longevity owing to greater cell numbers and divisions, which provide more opportunities for mutations. However, the perceived lack of such associations across species, named ‘Peto’s paradox’, suggests th...
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| Format: | Article |
| Language: | English |
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The Royal Society
2025-07-01
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| Series: | Royal Society Open Science |
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| Online Access: | https://royalsocietypublishing.org/doi/10.1098/rsos.250840 |
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| author | Antoine M. Dujon Peter A. Biro Beata Ujvari Frédéric Thomas |
| author_facet | Antoine M. Dujon Peter A. Biro Beata Ujvari Frédéric Thomas |
| author_sort | Antoine M. Dujon |
| collection | DOAJ |
| description | The multistage carcinogenesis model predicts that cancer risk should increase with body size and longevity owing to greater cell numbers and divisions, which provide more opportunities for mutations. However, the perceived lack of such associations across species, named ‘Peto’s paradox’, suggests that larger or longer-lived animals may have evolved enhanced cancer suppression mechanisms. Empirical tests of this paradox have been limited by data availability, but large-scale zoo datasets now enable comparative analyses of cancer prevalence in vertebrates. Currently used statistical methods, however, often fail to adequately account for uncertainty in key model parameters. In this study, we use Bayesian methods to reanalyse these datasets and explore Peto’s paradox, emphasizing the importance of quantifying uncertainty in comparative oncology. Our results show that body mass is positively associated with malignancy risk in mammals and amphibians, while it is negatively associated with cancer mortality in mammals. Longevity is positively associated with malignancy risk in non-avian sauropsids and amphibians. However, these relationships are accompanied by effect sizes with substantial uncertainty, primarily owing to small sample sizes. Through simulations, we demonstrate the limitations of current datasets and models. We also discuss the broader implications of Peto’s paradox and suggest recommendations for improving future research on cancer risk across species. |
| format | Article |
| id | doaj-art-a49cd279a5fa44b784a883941d6d54fd |
| institution | DOAJ |
| issn | 2054-5703 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Royal Society Open Science |
| spelling | doaj-art-a49cd279a5fa44b784a883941d6d54fd2025-08-20T02:47:24ZengThe Royal SocietyRoyal Society Open Science2054-57032025-07-0112710.1098/rsos.250840Towards a more robust comparative oncology: a Bayesian reanalysis of Peto’s paradox and discussion of comparative cancer risk studies in vertebratesAntoine M. Dujon0Peter A. Biro1Beata Ujvari2Frédéric Thomas3School of Life and Environmental Sciences, Deakin University, Waurn Ponds, Victoria 3216, AustraliaSchool of Life and Environmental Sciences, Deakin University, Waurn Ponds, Victoria 3216, AustraliaSchool of Life and Environmental Sciences, Deakin University, Waurn Ponds, Victoria 3216, AustraliaCREEC/(CREES), MIVEGEC, Unité Mixte de Recherches, IRD 224–CNRS 5290, Université de Montpellier, Montpellier, FranceThe multistage carcinogenesis model predicts that cancer risk should increase with body size and longevity owing to greater cell numbers and divisions, which provide more opportunities for mutations. However, the perceived lack of such associations across species, named ‘Peto’s paradox’, suggests that larger or longer-lived animals may have evolved enhanced cancer suppression mechanisms. Empirical tests of this paradox have been limited by data availability, but large-scale zoo datasets now enable comparative analyses of cancer prevalence in vertebrates. Currently used statistical methods, however, often fail to adequately account for uncertainty in key model parameters. In this study, we use Bayesian methods to reanalyse these datasets and explore Peto’s paradox, emphasizing the importance of quantifying uncertainty in comparative oncology. Our results show that body mass is positively associated with malignancy risk in mammals and amphibians, while it is negatively associated with cancer mortality in mammals. Longevity is positively associated with malignancy risk in non-avian sauropsids and amphibians. However, these relationships are accompanied by effect sizes with substantial uncertainty, primarily owing to small sample sizes. Through simulations, we demonstrate the limitations of current datasets and models. We also discuss the broader implications of Peto’s paradox and suggest recommendations for improving future research on cancer risk across species.https://royalsocietypublishing.org/doi/10.1098/rsos.250840cancerphylogenieevolutionary mismatchzoo animalscancer riskscientific method |
| spellingShingle | Antoine M. Dujon Peter A. Biro Beata Ujvari Frédéric Thomas Towards a more robust comparative oncology: a Bayesian reanalysis of Peto’s paradox and discussion of comparative cancer risk studies in vertebrates Royal Society Open Science cancer phylogenie evolutionary mismatch zoo animals cancer risk scientific method |
| title | Towards a more robust comparative oncology: a Bayesian reanalysis of Peto’s paradox and discussion of comparative cancer risk studies in vertebrates |
| title_full | Towards a more robust comparative oncology: a Bayesian reanalysis of Peto’s paradox and discussion of comparative cancer risk studies in vertebrates |
| title_fullStr | Towards a more robust comparative oncology: a Bayesian reanalysis of Peto’s paradox and discussion of comparative cancer risk studies in vertebrates |
| title_full_unstemmed | Towards a more robust comparative oncology: a Bayesian reanalysis of Peto’s paradox and discussion of comparative cancer risk studies in vertebrates |
| title_short | Towards a more robust comparative oncology: a Bayesian reanalysis of Peto’s paradox and discussion of comparative cancer risk studies in vertebrates |
| title_sort | towards a more robust comparative oncology a bayesian reanalysis of peto s paradox and discussion of comparative cancer risk studies in vertebrates |
| topic | cancer phylogenie evolutionary mismatch zoo animals cancer risk scientific method |
| url | https://royalsocietypublishing.org/doi/10.1098/rsos.250840 |
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