In the evolving world of cancer research, scientists have been studying why some animals like elephants get cancer at much lower rates than other mammals.
Researchers at the National Institutes of Health (NIH) tell us that cancer is caused by genetic changes, or deoxyribonucleic acid (DNA) mutations that allow cells to grow and divide uncontrollably. Factors known to damage DNA include ultra-violet (UV) light and tobacco smoke, along with the cellular mechanisms of DNA repair.
Cells also naturally accumulate a certain number of mutations with each division. If all mammalian cells were equally susceptible to mutations that could lead to cancer, then cancer risk should increase with body size (greater number of cells) and species life span (greater number of cell divisions). However, many large animals with long life spans, such as elephants, don’t appear to have higher rates of cancer. [Ref 1]
Common risk factors for cancer include alcohol consumption, exposure to cancer-causing substances, chronic inflammation, diet, hormones, immunosuppression, infectious agents, obesity, radiation, sunlight and tobacco. Scientists have recommended limiting exposure to these risk factors to avoid the development of cancer in the body.
A University of Utah research team led by Dr. Joshua Schiffman is examining cancer rates in different species. They began by studying 14 years of autopsy data collected by the San Diego Zoo. They analyzed 36 species that spanned up to 6 orders of magnitude in size and life span—ranging from the 51-gram striped grass mouse, which lives a maximum of 4.5 years, to the elephant, which can live up to 65 years. They also analyzed 644 documented deaths from a global database of captive African and Asian elephants.
African elephants are the world’s largest land animals. The biggest can be up to 7.5 m long, 3.3 m high at the shoulder, and 6 tonnes in weight.
Usually, a single calf is born after a gestation period of 22 months. Young elephants wean after 6 to 18 months, although they may continue nursing for over 6 years.
Elephants live up to around 70 years, with females mostly fertile between 25 and 45. Males need to reach 20 years of age in order to successfully compete for mating. The other notable feature of African elephants is their very large ears, which allow them to radiate excess heat. [Source: World Wildlife Federation]
To date, Schiffman’s team has found that there is no significant relationship between cancer risk and body size, life span, or basic metabolic rate among the species. For elephants, they estimated that the overall lifetime chance of dying from cancer was less than 5%. The lifetime cancer mortality rate for humans, in contrast, is about 20%.
Research team members have looked at the genome of this large mammal to better understand how elephants avoid cancer. More specifically, their research focused on the P53 gene. TP53 codes for the protein p53, a crucial tumor suppressor that stops cells with damaged DNA from dividing. People have 2 alleles (copies) of TP53. One is inherited from each parent, and both are crucial to prevent cancer.
TP53 is mutated in most human cancers. Having only one functional allele causes Li-Fraumeni syndrome, which is characterized by a more than 90% lifetime risk of cancer.
Interestingly, analysis of the genomic sequence show that African elephants have at least 40 TP53 alleles. Functional assays comparing elephant and human cells showed that in response to DNA damage, cells from elephants had higher cell death (apoptosis) rates but didn’t boost DNA repair mechanisms. Both are known p53-mediated responses to DNA damage. Cells obtained from people with Li-Fraumeni syndrome had significantly less apoptosis than the human controls and more than 5 times less than elephants. [Ref 1]
These results suggest that elephants may have evolved to resist cancer by triggering apoptosis through p53 to efficiently remove mutant cells.
“Nature has already figured out how to prevent cancer,” Schiffman says. “It’s up to us to learn how different animals tackle the problem so we can adapt those strategies to prevent cancer in people.”
Understanding how elephants and other species have evolved to suppress cancer may prove helpful to scientists and researchers. These discovers may enable new strategies for prevention and treatment of cancer and other diseases.
- How Elephants Defend Against Cancer, by Harrison Wein, PhD for NIH Research Matters, October 26, 2015, http://www.nih.gov/news-events/nih-research-matters/how-elephants-defend-against-cancer