Why elephants rarely get cancer is a mystery that has stumped scientists for decades. A study published in October in the Journal of the American Medical Association, as the result of a collaboration between Primary Children’s Hospital, Utah’s Hogle Zoo, Huntsman Cancer Institute at the University of Utah and the Ringling Bros. Center for Elephant Conservation, found 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.
Further, elephants may 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. “Nature has already figured out how to prevent cancer,” says co-senior author Joshua Schiffman, M.D., pediatric oncologist at Huntsman Cancer Institute, University of Utah School of Medicine, and Primary Children’s Hospital. It’s up to us to learn how different animals tackle the problem, so we can adapt those strategies to prevent cancer in people.”
According to Schiffman, elephants have long been considered a walking conundrum. Because they have 100 times as many cells as people, they should be 100 times more likely to have a cell slip into a cancerous state and trigger the disease over their long life span of 50 to 70 years.
And yet it’s believed that elephants get cancer less often, a theory confirmed in this study. Analysis of a large database of elephant deaths estimates a cancer mortality rate of less than 5 percent compared to 11 percent to 25 percent in people.
Researchers 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: they committed suicide. “It’s as if the elephants said, ‘It’s so important that we don’t get cancer, we’re going to kill this cell and start over fresh,’” says Schiffman. “If you kill the damaged cell, it’s gone, and it can’t turn into cancer.
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,” says Schiffman. “We think that making more p53 is nature’s way of keeping this species alive.” Additional studies will be needed to determine whether p53 directly protects elephants from cancer.
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