Why cancer is rare in elephants decoded

Elephants have extra copies of a gene that encodes a tumour suppressor and also have a more robust mechanism for killing damaged cells that are at risk for becoming cancerous, scientists have found, solving a decades old mystery of why elephants rarely get cancer.

Researchers found that elephants have 38 additional modified copies (alleles) of a gene that encodes p53, a well-defined tumour 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 per cent 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. It's up to us to learn how different animals tackle the problem so we can adapt those strategies to prevent cancer in people," said co-senior author Joshua Schiffman, pediatric oncologist at Huntsman Cancer Institute, University of Utah School of Medicine, and Primary Children's Hospital.

Since elephants 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.

Analysis of a large database of elephant deaths estimates a cancer mortality rate of less than 5 per cent compared to 11 to 25 per cent in people.

The scientists combed 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.

The vast majority, 38 of them, are so-called retrogenes, modified duplicates that have been churned out over evolutionary time.

Schiffman's team collaborated with Utah's Hogle Zoo and Ringling Bros Centre 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 - they committed suicide.

"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," said Schiffman.

"We think that making more p53 is nature's way of keeping this species alive," he said. Additional studies will be needed to determine whether p53 directly protects elephants from cancer, researchers said. The study was published in the Journal of the American Medical Association.