Understanding Why Elephants Rarely Get Cancer May Help Us Prevent it in Humans

Cancer is a devastating disease that has more than likely affected someone you know. In the US, a male has a 1 in 2 chance of developing cancer and a female has a 1 in 3 chance of developing cancer throughout the course of his or her life. Your risk of dying from cancer at any point in your lifetime is 1 in 4 if you are male and 1 in 5 if you are female. The most common cancers in both men and women are: lung, stomach, and colorectal cancer. In men, the list includes prostate and liver cancer, while in women the list includes breast and cervical cancer. Cancer is not exclusive to humans, in fact most animals in the world can get cancer.

As cells grow and divide they can accumulate mutations. Sometimes these mutations are harmless but sometimes they let the cells escape the normal mechanism that slows growth and allows them to rapidly grow and develop into a tumor. Cancer is not unique to humans. It has been seen in species all over the world but to varying levels of incidence. The general idea has been that if an animal is larger and lives longer it will have a higher incidence of cancer when compared to a smaller, shorter lived animal. The reasoning was that larger animals have more cells and animals that live longer have more cell divisions over the course of their life. This would increase the chance that they would develop a mutation that could lead to cancer. Interestingly, a research paper published in the Journal of the American Medical Association found that this wasn’t the case. In their work, there was no association between body size and life span, and cancer incidence rate. But why?

To understand the results we need to know a little bit about how cells normally deal with DNA damage and mutations. Inside a healthy cell, growth and division are tightly controlled by important proteins/mechanisms. Normally these proteins and mechanisms are efficient in repairing mutations however, if the mutation happens to affect one of these important proteins the protective mechanism will fail. Failure of these mechanisms allows cells to grow uncontrollably and develop into tumors and cancer. As a last resort to stop the cancer in its tracks, cells will commit suicide to stop the spread of the cancer. This is known as apoptosis and if it doesn’t work properly then the cancer cannot be stopped by our bodies.

When the researchers damaged the DNA in the cells of the elephants they noted that they committed suicide (apoptosis) at twice the rate of the human cells (14.6% vs. 7.2%). How come? What makes elephant cells more likely to kill themselves to stop harmful mutations? Turns out that the cells in elephants have many extra copies of a gene that codes for a very important protein. This protein is called p53 and it acts as a master switch that controls a cells growth and division. It has the very important job of stopping the cell from growing until all the damage to its DNA has been repaired. If it can’t be repaired, p53 tells the cell to undergo apoptosis in order to protect the organism. The elephants studied in this paper had up to 20 copies of the p53 gene. Humans only have two copies of the gene. These extra copies of the p53 gene ensure that even if one or two copies become mutated, the elephant will always have enough functioning p53 around.

What can we learn from this study? It reaffirms how important the p53 protein is to the prevention of cancer. p53 is so important in stopping cancer that there are people who suffer from a rare genetic disorder that have a 90% risk of getting cancer at any point in their life. The rare disease, Li-Fraumeni syndrome (LFS), occurs when one of their two copies of p53 is mutated and no longer works. The knowledge of how elephants control cancer adds to our growing understanding of how other animals prevent cancer. For example, the bowhead whale lives for 200 years and has duplications in many genes that help control cell growth and cancer. Naked mole rats live long, cancer free lives thanks to special variations in molecules that regulate cell growth. We don’t know why humans don’t have the same protective measures as other large animals, perhaps we had them at some point in our evolution and then lost them. If we can find molecules that mimic the same protective measures that exist in animals, including elephants, then we may be able to stop cancer from developing in the first place. This type of research shows the importance of turning to nature to help us answer some of our most challenging problems.

Photo Credit: “Two Elephants in Addo Elephant National Park” by Brian Snelson

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