Solutions to peto’s paradox revealed by mathematical modelling and cross-species cancer gene analysis

Aleah F. Caulin, Trevor A. Graham, Li San Wang, Carlo Maley

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish (US)
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Volume370
Issue number1673
DOIs
StatePublished - Jul 19 2015

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Neoplasm Genes
cancer
mathematical models
Genes
Whales
fold
whale
tumor
neoplasms
tumor suppressor genes
gene
Tumors
mutation
Tumor Suppressor Genes
whales
modeling
Neoplasms
genes
elephant
Clonal Evolution

Keywords

  • Algebraic model
  • Cancer
  • Evolution
  • Peto’s paradox
  • Tumour suppression
  • Wright–Fisher model

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Solutions to peto’s paradox revealed by mathematical modelling and cross-species cancer gene analysis. / Caulin, Aleah F.; Graham, Trevor A.; Wang, Li San; Maley, Carlo.

In: Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 370, No. 1673, 19.07.2015.

Research output: Contribution to journalArticle

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