A biological paradox offers new insights into the mystery of cancer


Carlo Maley is a researcher at Arizona State University’s Center for Biocomputing, Security, and Society. He is also a researcher at Arizona State University’s Biodesign Center for Immunotherapy, Vaccines, and Virotherapy, and the Biodesign Center for Evolutionary Mechanisms. Associate Professor of ASU’s Faculty of Life Sciences and Director of the Arizona Cancer Evolution Center.Credits: Arizona State University Biodesign Institute

The cells in the body can be thought of as targets for small archeries, each vulnerable to the deadly arrows of cancer. The more cells a given animal has, and the longer it lives, the more likely it is to accumulate harmful cell mutations that can ultimately lead to cancer. Or at least this is what intuition suggests.

Nevertheless, many very Big animal Having a huge cell population, including elephants and whales, not only survives into old age, but also cancer.. This biological mystery is named Peto’s Paradox.In short, the paradox says that Race Size and longevity should be proportional to the incidence of cancer, but actual cross-species data suggest that this association does not hold.

In a new study published in the journal NatureCarlo Maley, a researcher at the Center for Biocomputing, Security, and Society at Arizona State University, works with international colleagues to investigate the recent impact of Peto’s paradox and cancer throughout the tree of life. Emphasizes what science is learning about.

Researchers analyze the largest interspecific database of this species, the pool of adult mammal life from zoo records containing 110,148 individuals spanning 191 species.

The objectives could be to assess species-specific cancer mortality across a wide assortment of mammals, revisit Peto’s paradox claims in a rigorous quantitative manner, and relate to fighting disease in both humans and animals. It is about exploring a sexual cancer suppressor mechanism.

This study provides the most intensive assessment of Peto’s paradox to date. The findings provide conclusive evidence that the risk of death from cancer is largely independent of both species-wide body weight and life expectancy in adults.

The solution to the paradox lies in the fact that the larger size and evolution of lifespan of a species is accompanied by co-evolution of a powerful mechanism of cancer resistance.

Marie is also a researcher at Arizona State University’s Biodesign Center for Immunotherapy, Vaccines and Virotherapy and the Biodesign Center for Evolutionary Mechanisms. He is an associate professor of ASU’s Department of Life Sciences and director of the Arizona Cancer Evolution Center.

Constant battle

The fight against cancer has recorded a recent victory. Annual statistics for 2020 reveal the largest single-year reduction in cancer mortality ever recorded. American Cancer Society.. Despite significant advances in cancer diagnosis and treatment, the disease remains a major murderer, estimated to exceed 600,000 in the United States alone last year.

The tragedy is not limited to humans. Indeed, new studies report a significant cross-species cancer burden, especially among some human-caring mammals, and the number of cancer deaths in the adult population is staggering. It can reach 20-40%.

Cancer is a fact of life across the entire range of multicellular species on Earth, but the disease is hardly democratic in choosing its victims. Some species have a significantly higher or lower incidence of cancer because researchers are still working to solve puzzles.

A new study is investigating some surprises, including an unusually high cancer vulnerability in some carnivorous mammals. Inequality was found to be closely related to diet, with the highest cancer incidence in mammals consuming other mammals, but other factors also play an important role.

More cells, more problems?

Multicellular organisms, from simple to very complex, face challenges when cells divide. Cellular mutations can occur if the DNA copy mechanism cannot faithfully replicate the 6 billion base pairs of the genetic code. Environmental factors such as radiation can also compromise DNA integrity and cause mutations.

Most such mutations have no perceptible effect on the health of the organism. However, some cause catastrophic chain reactions, leading to cancer, often fatal pain.

This problem can be exacerbated as the organism grows and acquires more cells in the body. Another important factor is the accumulation of mutations over time, and age represents an important risk factor for cancer. This tendency is easily observed in a variety of species, including dogs and humans.

However, while this common-sense rule applies to certain species, researchers are quite different when looking at a wide variety of species, where large, long-lived species are often found to thrive in low-rate cancers. Look at things.

This apparent contradiction was first manifested by epidemiologist Richard Peto. He studied cancer incidence in humans and mice and found that the cancer incidence in the two species was about the same. This is a challenge given that humans have about 1000 times more cells than mice and live 30 times longer. Even more surprising is the observation that large, long-lived wildlife do not appear to be significantly more prone to cancer.

Nature faces the problem of cancer in large, long-lived species and seems to have arrived at many solutions that vary depending on the species involved. These tumor suppressor mechanisms may provide clues to control cancer in other animals, including humans.

Paradox survey

The basic insights of Peto’s paradox have long been recognized, but scientifically confirmed. So far, the available data have been inadequate in terms of sample size, age distribution, species association, and cause of death, and have not been able to draw firm conclusions in support of Peto’s paradox.

Current research utilizes a large data set called the Animal Information Management System (ZIMS). This dataset summarizes detailed information on age, gender, mortality / survival, and postmortem pathological data for adult non-domestic mammals. This abundant warehouse of cross-species information was important for a thorough analysis of Peto’s paradox.

A high cancer risk was observed in a zoo survey of carnivores. This may be due to the use of progestin or other forms of hormonal contraceptives, and postponement of pregnancy in zoo animals. Both factors are associated with the development of human cancer, as are non-domestic cats.

However, researchers have determined that contraception cannot fully explain the increased risk of cancer in carnivores. If possible, there is clear sexual prejudice in the data, and female carnivores show higher cancer incidence. Rather, the important determinant seems to be diet.

Meal as fate?

Carnivores usually eat a high-fat, low-fiber diet, which is known as a risk factor for cancer. Because carnivores are at the top of the food chain, they may ingest pollutants and other carcinogenic compounds at concentrated levels than animals that appear below the food chain.

In addition, meat consumption can expose carnivores to various pathogens associated with the process of cancer formation. Viruses in particular can pose a significant risk of cancer, and it is believed that 10-20% of all cancers are of viral origin.

Further analysis of zoo data reveals that among carnivores, carnivorous cancers that ingest other vertebrates as part of their normal diet compared to carnivores that consume little or no other mammals. It turned out that the incidence was the highest. The data suggest a high cost in terms of cancer risk in a carnivorous diet, especially a diet rich in mammalian prey.

Other factors that can affect the cancer incidence of these animals include low microbial flora diversity, degree of exercise in captivity, or other physiological factors. In contrast to carnivores, ruminants were found to have the lowest risk of cancer among mammals.

Talk to animals

The research results confirm the central assumptions of Peto’s paradox. The data show no significant association between cross-species cancer mortality risk and body weight, suggesting that natural selection of cancer resistance mechanisms in large animals significantly reduces the risk of carcinogenesis. ..

These various mechanisms have already been the focus of intensive research on the potential to prevent this deadly disease in both wildlife and humans, but many remain unclear. This study provides the basis for further research in this area and highlights the power of zoological data for future cancer research.

Cancer is a ubiquitous disease in mammals, studies conclude

For more information:
Orsolya Vincze, cancer risk across mammals, Nature (2021). DOI: 10.1038 / s41586-021-04224-5.. www.nature.com/articles/s41586-021-04224-5

Quote: The Biological Paradox is a Cancer Mystery Obtained on 22 December 2021 from https: //medicalxpress.com/news/2021-12-biological-paradox-insights-mystery-cancer.html (12 2021) Provides new insights to (22nd March)

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