Why Elephants Rarely Get Cancer: It’s in Their Genes

Why is cancer so rare in elephants? Scientists have observed this for decades, yet the explanation has eluded them until recently. Researchers at the University of Utah’s Huntsman Cancer Institute (HCI) and Arizona State University discovered elephants have extra copies of genes encoding p53, a tumor suppressor, and more robust apoptosis (programmed cell death) of damaged cells that may lead to cancer. According to the authors, these findings may aid future development of anti-cancer therapies in humans.

Because elephants have 100 times as many cells as humans, they should be much more likely to acquire cell damage that leads to cancer over a decades-long lifespan, according to co-senior author Dr. Joshua Schiffman. However, analysis of a large database of elephant deaths indicated the cancer mortality rate is less than 5 percent in elephants—much lower than the 11 to 25 percent observed in humans.

To investigate possible explanations, scientists from HCI, Primary Children’s Hospital, Hogle Zoo (based in Utah), and the Ringling Bros. Center for Elephant Conservation embarked on a collaborative effort that spanned several years. Combing through the African elephant genome revealed at least 40 additional modified gene alleles encoding p53, which is substantially more than the two found in humans. Thirty-eight of these alleles are “retrogenes”, modified duplicates that have developed over the evolutionary course. Schiffman and colleagues hypothesize that evolutionary development of these retrogenes may have helped increase cancer resistance in the elephants.

To further test whether these additional alleles protected the elephants from cancer, the researchers extracted white blood cells from elephants, healthy humans, and humans with Li-Fraumeni Syndrome (LFS), in which individuals have one working copy of p53 and are prone to developing cancer. Elephant cells subjected to radiation- or doxorubicin-induced DNA damage exhibited greater rates of apoptosis than those from healthy humans, who in turn had higher rates than those from patients with LFS. The scientists propose that the additional p53 in elephants induced programmed death of damaged cells that could promote cancer. Although further research will investigate whether the p53 directly protects the elephants from cancer, the authors suggest the present findings are instrumental for investigating both human and elephant cancer biology.

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