One of the mysteries that has stumped scientists for decades is the fact that elephants rarely get cancer. Researchers at Huntsman Cancer Institute at the University of Utah and Arizona State University, along with researchers from the Ringling Bros. Center for Elephant Conservation, recently looked for the answer. The results are published in the Journal of the American Medical Association.
Since elephants have 100 times as many cells as people, they should be 100 times more likely to have a cell skip into a cancerous state and trigger the disease over their life span, which typically is 50 to 70 years. But the researchers confirmed in the study that elephants get cancer less often. For the study, they analyzed a large database of elephant deaths with an estimated cancer mortality of less than five percent compared to the 11 to 25 percent in people.
The scientists went through the African elephant genome and found at least 40 copies of genes that code for p53, a protein well known for its cancer-inhibiting properties. DNA analysis provides clues as to why elephants have so many copies, a substantial increase over the two found in humans. The vast majority - 38 of them - are so-called retrogenes, modified duplicates that have been churned out over evolutionary time. The researchers determined that elephants have 38 additional modified copies (alleles) of a gene that encodes p53, a well-defined tumor suppressor, as compared to humans, who have only two.
Elephants may also have a more robust mechanism for killing damaged cells that are at risk for becoming cancerous. In isolated elephant cells, this activity is doubled compared to healthy human cells, and five times that of cells from patients with Li-Fraumeni Syndrome, who have only one working copy of p53 and more than a 90 percent lifetime cancer risk in children and adults. The results suggest extra p53 could explain elephants enhanced resistance to cancer.
The team collaborated with Utahs Hogle Zoo and Ringling Bros. Center for Elephant Conservation to test whether the extra gene copies may protect elephants from cancer. They extracted white blood cells from blood drawn from the animals during routine wellness checks and subjected the cells to treatments that damage DNA, a cancer trigger. In response, the cells reacted to damage with a characteristic p53-mediated response which means they committed suicide.
Nature has already figured out how to prevent cancer, said co-senior author Joshua Schiffman, M.D., pediatric oncologist at Huntsman Cancer Institute, University of Utah School of Medicine, and Primary Children's Hospital. Its up to us to learn how different animals tackle the problem so we can adapt those strategies to prevent cancer in people. Its as if the elephants said, Its so important that we dont get cancer, were going to kill this cell and start over fresh.
If you kill the damaged cell, its gone, and it cant turn into cancer, Schiffman added. This may be more effective of an approach to cancer prevention than trying to stop a mutated cell from dividing and not being able to completely repair itself. By all logical reasoning, elephants should be developing a tremendous amount of cancer, and in fact, should be extinct by now due to such a high risk for cancer. We think that making more p53 is natures way of keeping this species alive. Additional studies will be needed to determine whether p53 directly protects elephants from cancer.
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