A biological paradox provides new insights into the mystery of cancer

The cells in the body can be seen as tiny arrow targets, each of which is vulnerable to cancer deadly arrows

However, many large animals that carry a lot of cells, including elephants and whales, can not only live to old age, but the incidence of cancer is also very low

In a new study published in the journal Nature, Carlo Marley, a researcher at Arizona State University's Biodesign Center for Biocomputing, Security and Society (Biodesign Center for Biocomputing, Security and Society) Maley), together with his international colleagues, explored the latest meaning of Peto's paradox and emphasized the understanding of cancer in the tree of life by science

The researchers analyzed the largest cross-species database-an adult mammal database from the zoo, which includes 110,148 individuals of 191 species

Its purpose is to assess the species-specific cancer mortality of various mammals, re-examine the claims of Pitto's paradox in a rigorous and quantitative manner, and explore possible cancer suppression mechanisms related to humans and animals fighting diseases

This research provides the most in-depth evaluation of Peto's paradox to date

The solution to this paradox is that in species, the evolution of larger body sizes and longer lifespans has been accompanied by the co-evolution of powerful anti-cancer mechanisms

Maley is also a researcher at the Biological Design Center for Immunotherapy, Vaccine and Viral Therapy and the Biological Design Center for Evolutionary Mechanisms at Arizona State University

He is an associate professor in the College of Life Sciences at Arizona State University and the director of the Arizona Cancer Evolution Center

Constant battle

The fight against cancer has recently achieved some victories

This scourge is not limited to humans

Although cancer is a fact of life in all multicellular species on the planet, it is difficult for this disease to democratically choose its victims

This new study explores some surprising findings, including the unusually high cancer susceptibility of some carnivorous mammals

The more cells, the more problems?

Multicellular organisms, from simple to highly complex, face challenges in cell division

Most of these mutations have no obvious effect on the health of the organism

This problem will worsen when the organism becomes larger and gets more cells in the body

However, although this rule of common sense applies to specific species, researchers have discovered something quite different when looking at a wide range of different species.
Among these species, large, long-lived species tend to thrive and have a low incidence of cancer.

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This obvious contradiction was first proposed by epidemiologist Richard Pito
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He studied the incidence of cancer in humans and mice and found that the incidence of cancer in these two species is roughly the same
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Considering that the number of human cells is about 1,000 times that of mice, and the life span is 30 times that of mice, this creates a problem
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Even more surprising is the observation that large and long-lived wild animals do not seem to show a greater tendency for cancer
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It seems that nature has encountered cancer problems in large, long-lived species and has come up with some solutions, which vary according to the species involved
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These cancer suppression mechanisms may provide clues for suppressing cancer in other animals, including humans
.

Explore a paradox

Although the basic point of Peto's paradox has long been recognized, scientific verification is quite challenging
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So far, the existing data are not sufficient in terms of sample size, age distribution, species relevance, and causes of death, and it is impossible to draw conclusive conclusions in support of Peto's paradox
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The current research utilizes a large data set called the Animal Information Management System (ZIMS), which compiles detailed information about the age, sex, death/alive status, and postmortem pathology data of adult non-domestic mammals
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This wealth of cross-species information is essential to thoroughly analyze Peto’s paradox
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An investigation by the zoo found that carnivores have a high risk of cancer
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This may be due to the use of progesterone and other forms of hormonal contraception and delaying pregnancy in zoo animals
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Both of these factors are related to the development of human cancers and non-domestic cat cancers
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However, researchers believe that contraception does not fully explain the increased risk of cancer in carnivores
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If possible, the obvious gender bias in the data will be obvious, and the incidence of cancer in female carnivores is higher
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Instead, a key determinant seems to be diet
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Is food destiny?

Carnivores usually eat high-fat, low-fiber foods, which is a known risk factor for cancer
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Because carnivores are at the top of the food chain, they can ingest more concentrated pollutants or other carcinogenic compounds than animals at a lower part of the food chain
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In addition, eating meat exposes carnivores to various pathogens related to the process of cancer formation
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Viruses in particular have a considerable risk of causing cancer, and it is believed that 10-20% of all cancers come from viruses
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Further analysis of zoo data showed that among carnivores, carnivores that often eat other vertebrates have the highest risk of cancer compared with carnivores that rarely or never eat other mammals
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Data shows that carnivorous diets, especially diets rich in mammalian prey, pay a high price in terms of cancer risk
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Other factors that may affect the incidence of cancer in these animals include the low diversity of the microbial community, the degree of physical exercise in captivity, or other physiological factors
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Compared with carnivores, ruminants have the lowest cancer risk among mammals
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Talking with animals

The research results confirmed the core hypothesis of Peto's paradox
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The data shows that there is no significant relationship between the cancer death risk of different species and the body mass, which indicates that the natural selection of the anti-cancer mechanism of large animals is the reason for significantly reducing their carcinogenic risk
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These different mechanisms have become the focus of in-depth research because they have the potential to prevent this deadly disease in wild animals and humans, although there are still many unknowns
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This research provides a basis for further exploration in this field and emphasizes the role of zoology data for future cancer research
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Author: Richard Harth