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

Debate

Florence Bernex¹  Nelly Pirot¹  Beata Ujvari²  Eric Solary³  François Bonhomme⁴  François Renaud⁵  Frédéric Thomas⁵  Dorothée Misse⁵  Audrey Arnal⁵  Marion Vittecoq⁶  Benjamin Roche⁷  Hugo Ducasse⁸ 

[1] CREEC, 911 Avenue Agropolis, BP 64501, 34394, Montpellier Cedex 5, France;Université Montpellier, 163 rue Auguste Broussonnet, 34090, Montpellier, France;RHEM, Réseau d’Histologie Expérimentale de Montpellier, IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM, U1194 Montpellier France, Montpellier, France;ICM, 208 Avenue des Apothicaires, 34298, Montpellier, France;Centre for Integrative Ecology, School of Life and Environmental Sciences, Deakin University, Waurn Ponds, Vic, Australia;INSERM U1009, Université Paris-Sud, Gustave Roussy, Villejuif, France;ISEM, UMR CNRS/IRD/EPHE/UM 5554, Place Eugène Bataillon, 34095, Montpellier Cedex 5, France;MIVEGEC, UMR IRD/CNRS/UM 5290, 911 Avenue Agropolis, BP 64501, 34394, Montpellier Cedex 5, France;CREEC, 911 Avenue Agropolis, BP 64501, 34394, Montpellier Cedex 5, France;MIVEGEC, UMR IRD/CNRS/UM 5290, 911 Avenue Agropolis, BP 64501, 34394, Montpellier Cedex 5, France;CREEC, 911 Avenue Agropolis, BP 64501, 34394, Montpellier Cedex 5, France;Centre de Recherche de la Tour du Valat, 13200, Arles, Le Sambuc, France;MIVEGEC, UMR IRD/CNRS/UM 5290, 911 Avenue Agropolis, BP 64501, 34394, Montpellier Cedex 5, France;CREEC, 911 Avenue Agropolis, BP 64501, 34394, Montpellier Cedex 5, France;UMMISCO, UMI IRD/UPMC, 32 Avenue Henri Varagnat, 93143, Bondy Cedex, France;MIVEGEC, UMR IRD/CNRS/UM 5290, 911 Avenue Agropolis, BP 64501, 34394, Montpellier Cedex 5, France;CREEC, 911 Avenue Agropolis, BP 64501, 34394, Montpellier Cedex 5, France;Université Montpellier, 163 rue Auguste Broussonnet, 34090, Montpellier, France;

关键词: Cancer Prevalence;    Basal Metabolic Rate;    Beluga Whale;    Naked Mole Rate;    High Cancer Risk;   

DOI  :  10.1186/s12885-015-1782-z

 received in 2015-04-07, accepted in 2015-10-12,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundCarcinogenesis 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.DiscussionsHere 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.SummaryThe 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.

【 授权许可】

CC BY   
© Ducasse et al. 2015