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Can Peto's paradox be used as the null hypothesis to identify the role of evolution in natural resistance to cancer? A critical review

Ducasse, Hugo, Ujvari, Beata, Solary, Eric, Vittecoq, Marion, Arnal, Audrey, Bernex, Florence, Pirot, Nelly, Misse, Dorothee, Bonhomme, Francois, Renaud, Francois, Thomas, Frederic and Roche, Benjamin 2015, Can Peto's paradox be used as the null hypothesis to identify the role of evolution in natural resistance to cancer? A critical review, BMC cancer, vol. 15, pp. 1-9, doi: 10.1186/s12885-015-1782-z.

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Title Can Peto's paradox be used as the null hypothesis to identify the role of evolution in natural resistance to cancer? A critical review
Author(s) Ducasse, Hugo
Ujvari, BeataORCID iD for Ujvari, Beata orcid.org/0000-0003-2391-2988
Solary, Eric
Vittecoq, Marion
Arnal, Audrey
Bernex, Florence
Pirot, Nelly
Misse, Dorothee
Bonhomme, Francois
Renaud, Francois
Thomas, Frederic
Roche, Benjamin
Journal name BMC cancer
Volume number 15
Article ID 792
Start page 1
End page 9
Total pages 9
Publisher BioMed Central
Place of publication London, Eng.
Publication date 2015-10-24
ISSN 1471-2407
Keyword(s) Cancer
Natural resistance
Carcinogenesis
Science & Technology
Life Sciences & Biomedicine
Oncology
NAKED MOLE-RAT
ACUTE LYMPHOBLASTIC-LEUKEMIA
PARASITE SPECIES RICHNESS
MULTISTAGE CARCINOGENESIS
ULTRAVIOLET-RADIATION
ANTICANCER SELECTION
MUTATIONAL PROCESSES
GENETIC ALTERATIONS
GENOME SIZE
BODY-MASS
Summary BACKGROUND: Carcinogenesis affects not only humans but almost all metazoan species. Understanding the rules driving the occurrence of cancers in the wild is currently expected to provide crucial insights into identifying how some species may have evolved efficient cancer resistance mechanisms. Recently the absence of correlation across species between cancer prevalence and body size (coined as Peto's paradox) has attracted a lot of attention. Indeed, the disparity between this null hypothesis, where every cell is assumed to have an identical probability to undergo malignant transformation, and empirical observations is particularly important to understand, due to the fact that it could facilitate the identification of animal species that are more resistant to carcinogenesis than expected. Moreover it would open up ways to identify the selective pressures that may be involved in cancer resistance. However, Peto's paradox relies on several questionable assumptions, complicating the interpretation of the divergence between expected and observed cancer incidences.

DISCUSSIONS: Here we review and challenge the different hypotheses on which this paradox relies on with the aim of identifying how this null hypothesis could be better estimated in order to provide a standard protocol to study the deviation between theoretical/theoretically predicted and observed cancer incidence. We show that due to the disproportion and restricted nature of available data on animal cancers, applying Peto's hypotheses at species level could result in erroneous conclusions, and actually assume the existence of a paradox. Instead of using species level comparisons, we propose an organ level approach to be a more accurate test of Peto's assumptions.

SUMMARY: The accuracy of Peto's paradox assumptions are rarely valid and/or quantifiable, suggesting the need to reconsider the use of Peto's paradox as a null hypothesis in identifying the influence of natural selection on cancer resistance mechanisms.
Language eng
DOI 10.1186/s12885-015-1782-z
Field of Research 060305 Evolution of Developmental Systems
069999 Biological Sciences not elsewhere classified
1112 Oncology And Carcinogenesis
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30079910

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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.