As healthy as an elephant: why elephants rarely get cancer and what that means for cancer research.

Despite having a cell mass that is 100 times greater than humans and living, on average, through over 65 years of cellular divisions, less than 5% of deaths observed in African and Asian elephant populations is attributed to cancer. In comparison, the cancer mortality rate observed in humans is between 11% and 25%[1]. How can a species so large and long-lived be so “resistant” to malignancies? The answer is in their DNA.

Researchers at the Huntsman Cancer Institute at the University of Utah performed a genomic sequence analysis and examined cancer-related genes in elephants. Analysis revealed that elephant DNA contains 20 copies of TP53, a gene that encodes for the well-known tumor suppressor, p53. Humans, in contrast, only have one TP53 gene and both wildtype alleles are critical for proper p53 function; mutation of one human TP53 allele leads to Li-Fraument syndrome (LFS), a predisposition to cancer with a “90% lifetime risk for cancer, multiple primary tumors, and early childhood cancers” (Abegglen et al. E2).

Apoptosis and cell-cycle arrest after DNA damage was then examined in peripheral blood lymphocytes (PBLs) and fibroblasts of African and Asian elephants, healthy human controls, and individuals with LFS. All cells were exposed to varying dose and duration conditions of either ionizing radiation or doxorubicin, an anthracycline antibiotic that is used in cancer chemotherapy.

Greater p21 expression, which is stimulated by p53 to regulate cell-cycle progression, was observed in both elephant cell types compared to both human cell types following each condition of ionizing radiation. Reduced cell viability, indicative of cell-cycle arrest, was also observed in elephant cells following DNA damage. And most importantly, a direct relationship between doxorubicin and ionizing radiation-induced apoptosis and the number of wildtype TP53 alleles was also evident; elephant cells exposed to the DNA-damaging test conditions self-destructed at a rate two times greater than that of healthy human cells and more than five times greater than the rate of Li-Fraumeni cells (14.6%, 7.2%, and 2.7%, repectively).

Researchers concluded that TP53 retrogenes increase p53-dependent apoptosis in elephants, preventing the propagation of oncogenic mutations within the species. This study provides great insight into how TP53 quantity affects elephant cancer rates and may influence new, evolutionary-based approaches to the mechanisms of cancer suppression.

Retired Ringling Bros. circus elephants have an important new role! (video): http://www.sciencedaily.com/videos/9e3c96375ce6a8deae5f651ee0baf494.htm

And here is the link to the study: 

http://jama.jamanetwork.com/article.aspx?articleid=2456041

1.     Abegglen LM, Caulin AF, Chan A, et al. Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans.JAMA. Published online October 08, 2015. doi:10.1001/jama.2015.13134.