Solving Peto’s Paradox with Elephant Cancer Resistance
Why aren’t large and long-lived animals plagued with cancer? Large animals have many more cells, so if each cell had an equal chance of becoming cancerous, the organisms with more cells should be much more cancer-prone, especially when lifespans are long. Humans have 11% to 25% cancer mortality while elephants, despite having many, many more cells than us, have only about 5% cancer mortality. But, there is actually no demonstrable correlation between body size and cancer risk. This is known as “Peto’s Paradox¹”.
Lisa M. Abegglen and others² analyzed elephant genomes to study their cancer resistance mechanisms. Her team found that the African elephant genome contains 20 copies of TP53, a gene that codes for an important protein involved in preventing cancer; protein p53. This protein is called “the guardian of the genome” because it can activate DNA repair proteins, halt the cell cycle, or initiate apoptosis (cell suicide) before damaged DNA causes cancerous growth. Unfortunately, humans only have 1 copy per parent. When one inherits a bad copy of TP53 from a parent, they are at much higher risk of cancer. Elephants do not have this problem.
The elephants’ extra genes appear to heighten the apoptosis cell response to DNA damage. The study found that elephant cells were “twice as sensitive to DNA damage-induced apoptosis as human cells,” meaning that elephant cells are more likely to activate their own “kill-switch” when the DNA is damaged. This sacrifice quickly prevents cancerous cells from spreading throughout the body.
However, we cannot just assume that the extra TP53 genes actually produce the cancer preventing protein (p53). Why not? The researchers explain in their article that they believe not all of the extra copies of the gene may actually produce the protein. However, from the findings we can speculate that these elephants’ extra genes may soon solve Peto’s Paradox.
¹ Peto, R., F. J. Roe, P. N. Lee, L. Levy, and J. Clack. “Cancer and ageing in mice and men.” British Journal of Cancer 32, no. 4 (1975): 411.
² Abegglen, Lisa M., Aleah F. Caulin, Ashley Chan, Kristy Lee, Rosann Robinson, Michael S. Campbell, Wendy K. Kiso et al. “Potential mechanisms for cancer resistance in elephants and comparative cellular response to DNA damage in humans.” Jama 314, no. 17 (2015): 1850–1860
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