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      Towards cancer-aware life-history modelling

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          Abstract

          Studies of body size evolution, and life-history theory in general, are conducted without taking into account cancer as a factor that can end an organism's reproductive lifespan. This reflects a tacit assumption that predation, parasitism and starvation are of overriding importance in the wild. We argue here that even if deaths directly attributable to cancer are a rarity in studies of natural populations, it remains incorrect to infer that cancer has not been of importance in shaping observed life histories. We present first steps towards a cancer-aware life-history theory, by quantifying the decrease in the length of the expected reproductively active lifespan that follows from an attempt to grow larger than conspecific competitors. If all else is equal, a larger organism is more likely to develop cancer, but, importantly, many factors are unlikely to be equal. Variations in extrinsic mortality as well as in the pace of life—larger organisms are often near the slow end of the fast–slow life-history continuum—can make realized cancer incidences more equal across species than what would be observed in the absence of adaptive responses to cancer risk (alleviating the so-called Peto's paradox). We also discuss reasons why patterns across species can differ from within-species predictions. Even if natural selection diminishes cancer susceptibility differences between species, within-species differences can remain. In many sexually dimorphic cases, we predict males to be more cancer-prone than females, forming an understudied component of sexual conflict.

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          Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions.

          Some tissue types give rise to human cancers millions of times more often than other tissue types. Although this has been recognized for more than a century, it has never been explained. Here, we show that the lifetime risk of cancers of many different types is strongly correlated (0.81) with the total number of divisions of the normal self-renewing cells maintaining that tissue's homeostasis. These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to "bad luck," that is, random mutations arising during DNA replication in normal, noncancerous stem cells. This is important not only for understanding the disease but also for designing strategies to limit the mortality it causes. Copyright © 2015, American Association for the Advancement of Science.
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            The moulding of senescence by natural selection.

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              The evolution of body size: what keeps organisms small?

              It is widely agreed that fecundity selection and sexual selection are the major evolutionary forces that select for larger body size in most organisms. The general, equilibrium view is that selection for large body size is eventually counterbalanced by opposing selective forces. While the evidence for selection favoring larger body size is overwhelming, counterbalancing selection favoring small body size is often masked by the good condition of the larger organism and is therefore less obvious. The suggested costs of large size are: (1) viability costs in juveniles due to long development and/or fast growth; (2) viability costs in adults and juveniles due to predation, parasitism, or starvation because of reduced agility, increased detectability, higher energy requirements, heat stress, and/or intrinsic costs of reproduction; (3) decreased mating success of large males due to reduced agility and/or high energy requirements; and (4) decreased reproductive success of large females and males due to late reproduction. A review of the literature indicates a substantial lack of empirical evidence for these various mechanisms and highlights the need for experimental studies that specifically address the fitness costs of being large at the ecological, physiological, and genetic levels. Specifically, theoretical investigations and comprehensive case studies of particular model species are needed to elucidate whether sporadic selection in time and space is sufficient to counterbalance perpetual and strong selection for large body size.
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                Author and article information

                Journal
                Philos Trans R Soc Lond B Biol Sci
                Philos. Trans. R. Soc. Lond., B, Biol. Sci
                RSTB
                royptb
                Philosophical Transactions of the Royal Society B: Biological Sciences
                The Royal Society
                0962-8436
                1471-2970
                19 July 2015
                19 July 2015
                : 370
                : 1673 , Theme issue ‘Cancer across life: Peto's paradox and the promise of comparative oncology’ compiled and edited by Joshua Schiffman, Carlo C. Maley, Leonard Nunney, Michael Hochberg and Matthew Breen
                : 20140234
                Affiliations
                [1 ]Wissenschaftskolleg zu Berlin, Institute for Advanced Study , Wallotstrasse 19, Berlin 14193, Germany
                [2 ]Institute of Evolutionary Biology and Environmental Studies, University of Zurich , Winterthurerstrasse 190, Zurich 8057, Switzerland
                [3 ]Institut des Sciences de l'Evolution, Université Montpellier , UMR5554 du CNRS, Montpellier 34095, France
                [4 ]Santa Fe Institute , 1399 Hyde Park Road, Santa Fe, NM 87501, USA
                Author notes
                Article
                rstb20140234
                10.1098/rstb.2014.0234
                4581035
                26056356
                da3b19f8-bdec-4a5b-9b7c-83d47216db17

                © 2015 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.

                History
                : 14 April 2015
                Categories
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                Custom metadata
                July 19, 2015

                Philosophy of science
                peto′s paradox,cancer,life history,body size,sexual conflict,coevolution
                Philosophy of science
                peto′s paradox, cancer, life history, body size, sexual conflict, coevolution

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