Resolving Peto’s paradox: Modeling the potential effects of size‐related metabolic changes, and of the evolution of immune policing and cancer suppression
The intrinsic risk of cancer increases with body size and longevity; however, big long-lived species do not exhibit this increase, a contradiction named Peto's paradox. Five hypotheses potentially resolving this paradox were modeled using the multistage model of carcinogenesis. The five hypothe...
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ftcdlib:oai:escholarship.org:ark:/13030/qt9wj2m5cm 2023-11-05T03:40:57+01:00 Resolving Peto’s paradox: Modeling the potential effects of size‐related metabolic changes, and of the evolution of immune policing and cancer suppression Nunney, Leonard 1581 - 1592 2020-08-01 application/pdf https://escholarship.org/uc/item/9wj2m5cm unknown eScholarship, University of California qt9wj2m5cm https://escholarship.org/uc/item/9wj2m5cm public Evolutionary Applications, vol 13, iss 7 Biological Sciences Ecology Evolutionary Biology Genetics Cancer Aging Aetiology 2.1 Biological and endogenous factors blue whale body size cancer suppression elephant evolution immune policing multistage carcinogenesis somatic mutation Medicinal and Biomolecular Chemistry article 2020 ftcdlib 2023-10-09T18:05:59Z The intrinsic risk of cancer increases with body size and longevity; however, big long-lived species do not exhibit this increase, a contradiction named Peto's paradox. Five hypotheses potentially resolving this paradox were modeled using the multistage model of carcinogenesis. The five hypotheses were based on (1) intrinsic changes in metabolic rate with body size; adaptive increase in immune policing of (2) cancer cells or (3) cells with driver mutations; or adaptive increase in cancer suppression via (4) decreased somatic mutation rate, or (5) increased genetic control. Parameter changes needed to stabilize cancer risk in three types of cancer were estimated for tissues scaled from mouse size and longevity to human and blue whale levels. The metabolic rate hypothesis alone was rejected due to a conflict between the required interspecific effect with the observed intraspecific effect of size on cancer risk, but some metabolic change was optionally incorporated in the other models. Necessary parameter changes in immune policing and somatic mutation rate far exceeded values observed; however, natural selection increasing the genetic suppression of cancer was generally consistent with data. Such adaptive increases in genetic control of cancers in large and/or long-lived animals raise the possibility that nonmodel animals will reveal novel anticancer mechanisms. Article in Journal/Newspaper Blue whale University of California: eScholarship |
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Open Polar |
collection |
University of California: eScholarship |
op_collection_id |
ftcdlib |
language |
unknown |
topic |
Biological Sciences Ecology Evolutionary Biology Genetics Cancer Aging Aetiology 2.1 Biological and endogenous factors blue whale body size cancer suppression elephant evolution immune policing multistage carcinogenesis somatic mutation Medicinal and Biomolecular Chemistry |
spellingShingle |
Biological Sciences Ecology Evolutionary Biology Genetics Cancer Aging Aetiology 2.1 Biological and endogenous factors blue whale body size cancer suppression elephant evolution immune policing multistage carcinogenesis somatic mutation Medicinal and Biomolecular Chemistry Nunney, Leonard Resolving Peto’s paradox: Modeling the potential effects of size‐related metabolic changes, and of the evolution of immune policing and cancer suppression |
topic_facet |
Biological Sciences Ecology Evolutionary Biology Genetics Cancer Aging Aetiology 2.1 Biological and endogenous factors blue whale body size cancer suppression elephant evolution immune policing multistage carcinogenesis somatic mutation Medicinal and Biomolecular Chemistry |
description |
The intrinsic risk of cancer increases with body size and longevity; however, big long-lived species do not exhibit this increase, a contradiction named Peto's paradox. Five hypotheses potentially resolving this paradox were modeled using the multistage model of carcinogenesis. The five hypotheses were based on (1) intrinsic changes in metabolic rate with body size; adaptive increase in immune policing of (2) cancer cells or (3) cells with driver mutations; or adaptive increase in cancer suppression via (4) decreased somatic mutation rate, or (5) increased genetic control. Parameter changes needed to stabilize cancer risk in three types of cancer were estimated for tissues scaled from mouse size and longevity to human and blue whale levels. The metabolic rate hypothesis alone was rejected due to a conflict between the required interspecific effect with the observed intraspecific effect of size on cancer risk, but some metabolic change was optionally incorporated in the other models. Necessary parameter changes in immune policing and somatic mutation rate far exceeded values observed; however, natural selection increasing the genetic suppression of cancer was generally consistent with data. Such adaptive increases in genetic control of cancers in large and/or long-lived animals raise the possibility that nonmodel animals will reveal novel anticancer mechanisms. |
format |
Article in Journal/Newspaper |
author |
Nunney, Leonard |
author_facet |
Nunney, Leonard |
author_sort |
Nunney, Leonard |
title |
Resolving Peto’s paradox: Modeling the potential effects of size‐related metabolic changes, and of the evolution of immune policing and cancer suppression |
title_short |
Resolving Peto’s paradox: Modeling the potential effects of size‐related metabolic changes, and of the evolution of immune policing and cancer suppression |
title_full |
Resolving Peto’s paradox: Modeling the potential effects of size‐related metabolic changes, and of the evolution of immune policing and cancer suppression |
title_fullStr |
Resolving Peto’s paradox: Modeling the potential effects of size‐related metabolic changes, and of the evolution of immune policing and cancer suppression |
title_full_unstemmed |
Resolving Peto’s paradox: Modeling the potential effects of size‐related metabolic changes, and of the evolution of immune policing and cancer suppression |
title_sort |
resolving peto’s paradox: modeling the potential effects of size‐related metabolic changes, and of the evolution of immune policing and cancer suppression |
publisher |
eScholarship, University of California |
publishDate |
2020 |
url |
https://escholarship.org/uc/item/9wj2m5cm |
op_coverage |
1581 - 1592 |
genre |
Blue whale |
genre_facet |
Blue whale |
op_source |
Evolutionary Applications, vol 13, iss 7 |
op_relation |
qt9wj2m5cm https://escholarship.org/uc/item/9wj2m5cm |
op_rights |
public |
_version_ |
1781697182725832704 |