Why elephants hardly ever get cancer and how that can help us

“Elephants have enhanced defences against cancer that can prevent tumours forming,” BBC News reports.

Elephants have long been a puzzle to evolutionary biologists. Because of their large size, which means they have more cells that could potentially become cancerous, it would be expected they should have above-average cancer death rates – as we saw with the story about tall people last week.

But this is not the case. Just 1 in 20 elephants die of cancer, compared with around 1 in 5 humans. In this study, researchers wanted to see why this is and if there could be any human applications.

Researchers collected white blood cells from African and Asian elephants. They found elephants have at least 20 copies of a gene called TP53. TP53 is known to encourage cell “suicide” when DNA is damaged, stopping any potential cancer in its tracks. In contrast, humans are thought to have only a single copy of the TP53 gene.

Of course the big question – the elephant in the room, if you will – is how we can boost TP53 activity in humans to stimulate a similar protective effect. The simple answer is: we don’t know. Researchers have known about the effects of TP53 since 1979, but as yet have had little joy harnessing its effects.

Currently, prevention is better than cure. Proven methods to reduce your cancer risk include not smoking, eating a healthy diet that includes lots of fruit and vegetables, maintaining a healthy weight, taking regular exercise, avoiding sunburn, and moderating your consumption of alcohol.  

Where did the story come from?

The study was carried out by researchers from the University of Utah, the University of Pennsylvania, the Ringling Bros. and Barnum & Bailey Center for Elephant Conservation, Arizona State University, and the University of California.

It was funded by multiple US organisations, including the US Department of Energy, National Institutes of Health, Breast Cancer Research Program, and Huntsman Cancer Institute (HCI) Nuclear Control Program.

The study was published in the peer-reviewed Journal of the American Medical Association.

Overall, it was widely covered by the UK media, and was reported accurately and responsibly. However, some of the study’s limitations have not been explicitly explained.  

What kind of research was this?

This study was mainly lab-based, and aimed to compare cancer rates in different animals, identifying why some are more “cancer-resistant” than others.

Larger animals, such as elephants and lions, might be expected to get cancer more frequently than smaller ones, as they have more cells that can become cancerous. However, this is not generally the case – something described as Peto’s paradox.

This study focused on identifying why elephants were more cancer-resistant, by comparing how cells from elephants, healthy humans and cancer-prone patients respond to DNA damage, which can cause cells to become cancerous. The cancer-prone patients had Li-Fraumeni syndrome (LFS), a rare disorder that increases the risk of developing several types of cancer, particularly in children and young adults.

In-vitro or laboratory-based studies are good at understanding how individual cells respond to different exposures. However, as they only assess single cells in a controlled environment, the results may differ from inside a living organism, where many different cells are interacting in complex ways.   

What did the research involve?

The researchers first collected 14 years of data from San Diego Zoo animals to assess whether cancer rate is related to body size or lifespan. Data from the Elephant Encyclopaedia was also collected to analyse the cause of death in African and Asian elephants. The researchers used this data to calculate lifetime cancer risk as well as different species’ risk of dying from cancer.

Next, the researchers collected blood and extracted white blood cells from eight African and Asian elephants, 10 people with LFS and 11 people without a family history of cancer (healthy controls). They specifically looked at how many copies of the TP53 gene the different animal cells had. The TP53 gene produces a tumour-suppressing protein found in both humans and animals.

They also looked at how the cells responded when they were exposed to conditions that would damage the DNA in the cell. In these situations, if the cell does not stop dividing and either repair the DNA damage correctly or die by cell “suicide”, it could potentially become cancerous. 

What were the basic results?

A total of 36 mammalian species were analysed, which ranged from the very small – such as a grass mouse – to the very large (elephants), including humans. Some of the main results were that:

• cancer risk did not vary according to the body size or lifespan of the animals
• among the 644 elephants from the Elephant Encyclopaedia, about 3% developed cancer in their lifetime
• elephant white blood cells contained at least 20 copies of TP53 tumour-suppressing gene, whereas human cells only contain one copy of this gene
• there was evidence these extra copies of the gene were active
• cell response to DNA damage was significantly elevated in elephants when compared with humans
• cell suicide after DNA damage was more likely in elephants than cells from healthy humans, while cells from people with LFS were the least likely to undergo cell suicide after DNA damage  

How did the researchers interpret the results?

The researchers concluded that, “Compared with other mammalian species, elephants appeared to have a lower than expected rate of cancer, potentially related to multiple copies of TP53. Compared with human cells, elephant cells demonstrated increased [cell suicide] response following DNA damage.

“These findings, if replicated, could represent an evolutionary-based approach for understanding mechanisms related to cancer suppression.” 

Conclusion

This study assessed cancer risk across 36 mammals, and confirmed that incidence of cancer was not clearly related to the body size or lifespan of the animal. It then focused on looking at why elephants are more cancer-resistant than they would be expected to be, based on their size.

The researchers found elephants had 20 copies of a gene called TP53, which is responsible for suppressing tumours, whereas humans have only one copy.

Elephant cells in the lab were better than human cells at undergoing cell suicide when their DNA was damaged, protecting them from potentially cancer-causing mutations.

The results of this study are interesting and potentially shed some light on one reason why elephants have lower cancer rates than expected. It’s hoped that investigating the factors that underpin Peto’s paradox could one day lead to new treatments for humans.

However, this study looked at only one gene, whereas lots of genes are likely to be involved in the development of cancer, as well as environmental factors.

There is not much you can do about the genes you were born with, but there are steps you can take to reduce your cancer risk.

Links To The Headlines

Elephants’ low cancer rates explained. BBC News, October 9 2015

Could elephants help halt the spread of cancer? Animals found to carry huge number of genes that can stop the growth of tumours. Daily Mail, October 8 2015

Links To Science

Abegglen LM, Caulin AF, Chan A, et al. Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans. JAMA. Published online October 8 2015