Peto's paradox and the hallmarks of cancer: constructing an evolutionary framework for understanding the incidence of cancer

Nunney, Leonard; Muir, Brian Michael

doi:10.1098/rstb.2015.0161

Cited by 41 publications

(58 citation statements)

References 43 publications

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“…In fact, age is the strongest known risk factor for most cancer. [3] point out that Peto's paradox applies to the comparison of organs within a body. Organs with more stem cells and more cell turnover ought to have a higher incidence of cancer, and in general, they do [36].…”

Section: The Objectives Of This Issuementioning

confidence: 99%

“…The models used by Caulin et al [32], the algebraic models of Nunney [4] and Calabrese & Shibata [38] and a stochastic Fisher -Wright model [39] all assume neutral somatic evolution. So do the models of [3,37,40]. …”

Section: The Objectives Of This Issuementioning

confidence: 99%

“…Alternatively, we can view them from the perspective of the multicellular individual, where each hallmark reflects the failure of a set of defences that generally protect it from cancer [2,3]. In this conflict between the individual and its constituent cells, we can see two distinct adaptive processes, both driven by natural selection but showing a critically important difference: selection on cells operates at very much shorter time scale than selection on individuals.…”

Section: Introductionmentioning

confidence: 99%

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Peto's paradox and the promise of comparative oncology

Nunney

Maley

Breen

et al. 2015

Phil. Trans. R. Soc. B

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One contribution of 18 to a theme issue 'Cancer across life: Peto's paradox and the promise of comparative oncology'.Subject Areas: evolution, health and disease and epidemiology, molecular biology, physiology Keywords:Peto's paradox, comparative oncology, evolution, life-history theory, cancer, modelling The past several decades have seen a paradigm shift with the integration of evolutionary thinking into studying cancer. The evolutionary lens is most commonly employed in understanding cancer emergence, tumour growth and metastasis, but there is an increasing realization that cancer defences both between tissues within the individual and between species have been influenced by natural selection. This special issue focuses on discoveries of these deeper evolutionary phenomena in the emerging area of 'comparative oncology'. Comparing cancer dynamics in different tissues or species can lead to insights into how biology and ecology have led to differences in carcinogenesis, and the diversity, incidence and lethality of cancers. In this introduction to the special issue, we review the history of the field and outline how the contributions use empirical, comparative and theoretical approaches to address the processes and patterns associated with 'Peto's paradox', the lack of a statistical relationship of cancer incidence with body size and longevity. This burgeoning area of research can help us understand that cancer is not only a disease but is also a driving force in biological systems and species life histories. Comparative oncology will be key to understanding globally important health issues, including cancer epidemiology, prevention and improved therapies.

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Section: The Objectives Of This Issuementioning

confidence: 99%

Section: The Objectives Of This Issuementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Peto's paradox and the promise of comparative oncology

Nunney

Maley

Breen

et al. 2015

Phil. Trans. R. Soc. B

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“…These estimated risks vary by nearly four orders of magnitude-from less than 10 214 for small intestine adenocarcinoma, to approximately 10 211 for osteocarcinoma and thyroid cancers. An untested hypothesis to explain this variation is that the number of genetic or epigenetic alternations required to obtain cancers typical of different anatomical sites, differs in characteristic ways (see also Nunney & Muir [15]). …”

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confidence: 99%

Peto's paradox and human cancers

Noble

Kaltz

Hochberg

2015

Phil. Trans. R. Soc. B

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One contribution of 18 to a theme issue 'Cancer across life: Peto's paradox and the promise of comparative oncology'. Peto's paradox is the lack of the expected trend in cancer incidence as a function of body size and lifespan across species. The leading hypothesis to explain this pattern is natural selection for differential cancer prevention in larger, longer lived species. We evaluate whether a similar effect exists within species, specifically humans. We begin by reanalysing a recently published dataset to separate the effects of stem cell number and replication rate, and show that each has an independent effect on cancer risk. When considering the lifetime number of stem cell divisions in an extended dataset, and removing cases associated with other diseases or carcinogens, we find that lifetime cancer risk per tissue saturates at approximately 0.3 -1.3% for the types considered. We further demonstrate that grouping by anatomical site explains most of the remaining variation. Our results indicate that cancer risk depends not only on the number of stem cell divisions but varies enormously (approx. 10 000 times) depending on anatomical site. We conclude that variation in risk of human cancer types is analogous to the paradoxical lack of variation in cancer incidence among animal species and may likewise be understood as a result of evolution by natural selection.

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“…The large majority of cancers may be initiated by not yet fully-understood chemical processes denominated carcinogenesis [3]. Previous epidemiological studies have not found any relationship between cancer incidence, body size, and lifespan across species [5,6]. Over 15 types of key chemical and metabolic events have been associated with human carcinogens [3].…”

Section: Introductionmentioning

confidence: 99%

Cancer Risks Linked to the Bad Luck Hypothesis and Epigenomic Mutational Signatures

Belizário

2018

Epigenomes

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Exposure to pathogen infection, and occupational and environmental agents, contributes to induction of most types of cancer through different mechanisms. Cancer is defined and characterized by accumulation of mutations and epimutations that lead to changes in the cellular genome and epigenome. According to a recent Bad Luck Hypothesis, random error mutations during DNA replication in a small population of stem cells may be implicated in two-thirds of variation of cancer risk in 25 organs and tissues. What determines stem cell vulnerability and risk of malignancy across the spectrum of organs, such as the brain, bone marrow, skeletal muscles, skin, and liver? Have stem cells pooled in particular tissues or organs evolved some critical ability to deal with DNA damage in the presence of extrinsic environmental factors? This paper describes how the complex replication and repair DNA systems control mutational events. In addition, recent advances on cancer epigenomic signatures and epigenetic mechanisms are discussed, which will guide future investigation of the origin of cancer initiating cells in tissue and organs in a clinical setting.

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Peto's paradox and the hallmarks of cancer: constructing an evolutionary framework for understanding the incidence of cancer

Cited by 41 publications

References 43 publications

Peto's paradox and the promise of comparative oncology

Peto's paradox and the promise of comparative oncology

Peto's paradox and human cancers

Cancer Risks Linked to the Bad Luck Hypothesis and Epigenomic Mutational Signatures

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