Why elephants rarely get cancer?

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. 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. 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.

hey 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. Schiffman says, "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."

To test this, the researchers did a side-by-side comparison with cells isolated from elephants (n=8), healthy humans (n=10), and from patients with Li-Fraumeni Syndrome (n=10). They found that elephant cells exposed to radiation self-destruct at twice the rate of healthy human cells and more than five times the rate of Li-Fraumeni cells (14.6%, 7.2%, and 2.7%, respectively). These findings support the idea that more p53 offers additional protection against cancer.

Ref: Joshua D. Schiffman, MD et al. (2015) Potential mechanisms for cancer resistance in elephants and comparative cellular response to DNA damage in humans. JAMA.

DOI: 10.1001/jama.2015.13134