Cancer occurrence has shown significant variation across different vertebrate species, generally rising with larger adult body sizes and declining with extended gestation periods, according to findings published in Cancer Discovery, a journal of the American Association for Cancer Research (AACR).
Cancer occurrence has shown significant variation across various vertebrate species, and it tends to increase with larger adult size while decreasing with longer gestation periods, based on findings reported in Cancer Discovery, a journal of the American Association for Cancer Research (AACR).
Back in 1977, Sir Richard Peto, FRS, FAACR, proposed the idea that cancer rates in animals should correlate directly with their body size and lifespan. He suggested that larger animals might accumulate cellular damage more readily, and those with longer lifespans have more time to develop genetic mutations. However, he noted that this theory—known as Peto’s paradox—didn’t seem to hold true based on existing data.
Since then, researchers in comparative oncology have looked into what other elements might explain why certain species are more prone to cancer. “We aim to better understand what makes humans distinct in their cancer susceptibility,” stated Zachary Compton, PhD, a postdoctoral fellow in the University of Arizona Cancer Center’s NCI T32 fellowship program and the lead author of the study. “There’s an inherent cancer risk that seems to be part of our species, and comparative oncology can help us understand the reasons behind it.”
Research in comparative oncology has faced challenges due to limited sample sizes and species variety, which has constrained scientists’ insights regarding how growth and reproductive traits influence cancer development. Compton and his team gathered 16,049 necropsy records from 292 different species across 99 animal care facilities in the U.S. and London, focusing on species with at least 20 recorded necropsies. They evaluated the presence of neoplasia (uncontrolled cell growth) and identified which tissues were affected, creating a terminology dictionary from the neoplasia descriptions to help predict whether tumors were benign or malignant.
The overall median neoplasia prevalence across species was 4.89%, while malignancy was noted at 3.2%. Mammals exhibited the highest rates of both neoplasia (12%) and malignancy (7%), whereas amphibians recorded the lowest (1.2% and 0%, respectively). In comparison, about 39.3% of Americans will receive a cancer diagnosis during their lifetime, according to federal statistics. However, Compton cautioned that the exact malignancy rates in humans are unclear since most natural deaths do not involve autopsies, and there is a lack of reliable methods to estimate benign neoplasms at a population level.
A significant link was found between larger body size and higher neoplasia prevalence; specifically, with each tenfold increase in body mass, neoplasia risk rose by 2.1%. This finding presents a rare contradiction to Peto’s paradox, as described by Compton. Other factors associated with higher incidences of malignancy and/or neoplasia included greater maximum lifespan, bigger litter sizes in mammals, and, in a narrower analysis of 15 species, the somatic mutation rate, which indicates how quickly new mutations develop in the body. Conversely, longer gestation periods were correlated with a diminished prevalence of both neoplasia (a 5.3% reduction in neoplasia risk for every tenfold increase in gestation months) and malignancy (5.65% decrease in malignancy risk for the same increase).
Considering that longevity and gestation duration typically correlate with body size, the researchers carried out extra analyses that normalized the data based on these traits. When adjusting for gestation time, a stronger association was observed for body mass concerning neoplasia and malignancy prevalence—and this relationship held true for gestation time as well.
Compton acknowledged that understanding the intricate relationships between traits that do not evolve independently, like body mass and gestation duration, will necessitate further research. “Peto’s paradox is often discussed as a straightforward relationship between body size and cancer,” he remarked. “To genuinely grasp Peto’s paradox, we must consider the interconnections among various life history traits.”
On the topic of longevity, some researchers propose that neoplasia rates might be artificially high in human-managed populations, as animals in captivity tend to live much longer than in the wild. However, in this study, longevity did not show an independent correlation with rates of neoplasia or malignancy. Most species typically developed tumors within their natural lifespans, and the age at death was only linked to higher malignancy rates in amphibian species.
“We controlled for natural lifespan in our analysis and found that such control was unnecessary,” Compton explained. “The observed rates were not attributed to animals living longer in zoos.”
Lastly, the research identified species with notably high and low neoplasia rates. Ferrets and opossums had the highest rates, with 63% and 56% respectively being diagnosed with neoplasia during necropsies. In contrast, species exhibiting minimal neoplasia rates included the Nubian ibex, the tammar wallaby, and various bat species. Many species showed no malignancies, making them promising candidates for studying cancer suppression mechanisms, as described by Compton. He also mentioned that species with high neoplasia rates could serve as models for studying spontaneous cancer development and certain human cancer predisposition syndromes.
“This research opens the door to a variety of hypotheses we can explore, including the molecular pathways and environmental factors that may encourage or inhibit cancer development among these species,” Compton said.
However, the study does have limitations, such as the majority of the analyzed animals being cared for by humans rather than living in their natural habitats. Additionally, the necropsy records lacked comprehensive data about the animals’ environmental exposures or infections from cancer-related viruses, and certain cancers, like blood cancers, may also be challenging to detect during necropsies.
Funding for this research was provided by multiple organizations, including the National Institutes of Health, the CDMRP Breast Cancer Research Program, the Arizona Biomedical Research Commission, Hyundai Hope on Wheels, the Soccer for Hope Foundation, and several others, including support from France’s Agence Nationale de la Recherche and Région Nouvelle-Aquitaine for initiatives on ‘Cancer and Biodiversity.’
