ArticlePhilosophical transactions of the Royal Society of London. Series B, Biological sciences2015
Solutions to Peto's paradox revealed by mathematical modelling and cross-species cancer gene analysis.
Article in Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 98 citations in OpenAlex.
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- Extensive longevity and DNA virus-driven adaptation in nearcticbioRxiv : the preprint server for biology · 2025Article
- 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 · 2025Article
- Peto's paradox's relevance is off the scale.Aging · 2025Article
- Limited cell-autonomous anticancer mechanisms in long-lived bats.Nature communications · 2025Article
- Variable Gene Copy Number in Cancer-Related Pathways Is Associated With Cancer Prevalence Across Mammals.Molecular biology and evolution · 2025Article
- Cancer Prevalence across Vertebrates.Cancer discovery · 2025Article
- Revealing endogenous conditions for Peto's paradox via an ordinary differential equation model.Journal of mathematical biology · 2024Article
- Pervasive loss of regulated necrotic cell death genes in elephants, hyraxes, and sea cows (bioRxiv : the preprint server for biology · 2024Article
- Rapid evolution of genes with anti-cancer functions during the origins of large bodies and cancer resistance in elephants.bioRxiv : the preprint server for biology · 2024Article
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- Duplications of Human Longevity-Associated Genes Across Placental Mammals.Genome biology and evolution · 2023Article
- The NIH Comparative Genomics Resource: addressing the promises and challenges of comparative genomics on human health.BMC genomics · 2023Review
- Extinction scenarios in evolutionary processes: a multinomial Wright-Fisher approach.Journal of mathematical biology · 2023Article
- Evolutionary analysis of the mTOR pathway provide insights into lifespan extension across mammals.BMC genomics · 2023Article
- Cancer Prevalence Across Vertebrates.Research square · 2023Article
- Review
- Article
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Whales have 1000-fold more cells than humans and mice have 1000-fold fewer; however, cancer risk across species does not increase with the number of somatic cells and the lifespan of the organism. This observation is known as Peto's paradox. How much would evolution have to change the parameters of somatic evolution in order to equalize the cancer risk between species that differ by orders of magnitude in size? Analysis of previously published models of colorectal cancer suggests that a two- to three-fold decrease in the mutation rate or stem cell division rate is enough to reduce a whale's cancer risk to that of a human. Similarly, the addition of one to two required tumour-suppressor gene mutations would also be sufficient. We surveyed mammalian genomes and did not find a positive correlation of tumour-suppressor genes with increasing body mass and longevity. However, we found evidence of the amplification of TP53 in elephants, MAL in horses and FBXO31 in microbats, which might explain Peto's paradox in those species. Exploring parameters that evolution may have fine-tuned in large, long-lived organisms will help guide future experiments to reveal the underlying biology responsible for Peto's paradox and guide cancer prevention in humans.
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