Friday, October 9, 2015

Elephants and cancer

Elephants have enhanced defences against cancer that can prevent tumours forming, say scientists.
They were trying to explain why the animals have lower levels of cancer than would be expected by their size.

The team at the University of Utah said "nature has already figured out how to prevent cancer" and plan to devise new treatments.

But experts said the focus should be on the "ridiculous" and "absurd" things humans do to increase risk.

There is a train of thought that says every cell can become cancerous so the more of them you have, the more likely you are to get cancer.
So if an elephant has 100 times as many cells as a person then the trunk-swinging mammals should be 100 times more likely to have the disease.

And yet the analysis, published in the Journal of the American Medical Association, showed only 5% of elephants die from cancer compared to up to 25% of people...

But Prof Mel Greaves, from the Institute of Cancer Research in London, says we should focus on why humans have such high levels of cancer.

He told the BBC News website: "In terms of adaptive mechanisms against cancer we have the same as a chimp, but we get a lot more cancer than a chimp.

"I think the answer is humans are completely unique as a species in having very rapid social evolution in a short period of time."

He pointed to the rise of unhealthy, cancer-causing behaviours, such as obesity and sunbathing.
"You've never seen an elephant smoke!" he added.

The menopause is also a potential explanation for why humans have not evolved better ways of preventing cancer.

In an evolutionary sense "success" is judged by the number of descendants you have rather than how long you live.

Elephants have the greatest reproductive success towards the end of their lives, while humans can live for decades after the menopause.

It means there is little evolutionary pressure in humans to develop ways of preventing cancer in old age.

"Humans have engineered socially extended lifespans way beyond reproductive senescence - you can't find another species like that," concluded Prof Greaves.
Courtesy of:

Abegglen LM, Caulin AF, Chan A, Lee K, Robinson R, Campbell MS, Kiso WK,
Schmitt DL, Waddell PJ, Bhaskara S, Jensen ST, Maley CC, Schiffman JD. Potential
Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response
to DNA Damage in Humans. JAMA. 2015 Oct 8:1-11.



Evolutionary medicine may provide insights into human physiology and pathophysiology, including tumor biology.


To identify mechanisms for cancer resistance in elephants and compare cellular response to DNA damage among elephants, healthy human controls, and cancer-prone patients with Li-Fraumeni syndrome (LFS).

Design, Setting, and Participants:

A comprehensive survey of necropsy data was performed across 36 mammalian species to validate cancer resistance in large and long-lived organisms, including elephants (n = 644). The African and Asian elephant genomes were analyzed for potential mechanisms of cancer resistance. Peripheral blood lymphocytes from elephants, healthy human controls, and patients with LFS were tested in vitro in the laboratory for DNA damage response. The study included African and Asian elephants (n = 8), patients with LFS (n = 10), and age-matched human controls (n = 11). Human samples were collected at the University of Utah between June 2014 and July 2015.


Ionizing radiation and doxorubicin.

Main Outcomes and Measures:

Cancer mortality across species was calculated and compared by body size and life span. The elephant genome was investigated for alterations in cancer-related genes. DNA repair and apoptosis were compared in elephant vs human peripheral blood lymphocytes.


Across mammals, cancer mortality did not increase with body size and/or maximum life span (eg, for rock hyrax, 1% [95% CI, 0%-5%]; African wild dog, 8% [95% CI, 0%-16%]; lion, 2% [95% CI, 0%-7%]). Despite their large body size and long life span, elephants remain cancer resistant, with an estimated cancer mortality of 4.81% (95% CI, 3.14%-6.49%), compared with humans, who have 11% to 25% cancer mortality. While humans have 1 copy (2 alleles) of TP53, African elephants have at least 20 copies (40 alleles), including 19 retrogenes (38 alleles) with evidence of transcriptional activity measured by reverse transcription polymerase chain reaction. In response to DNA damage, elephant lymphocytes underwent p53-mediated apoptosis at higher rates than human lymphocytes proportional to TP53 status (ionizing radiation exposure: patients with LFS, 2.71% [95% CI, 1.93%-3.48%] vs human controls, 7.17% [95% CI, 5.91%-8.44%] vs elephants, 14.64% [95% CI, 10.91%-18.37%]; P < .001; doxorubicin exposure: human controls, 8.10% [95% CI, 6.55%-9.66%] vs elephants, 24.77% [95% CI, 23.0%-26.53%]; P < .001).

Conclusions and Relevance:

Compared with other mammalian species, elephants appeared to have a lower-than-expected rate of cancer, potentially related to multiple copies of TP53. Compared with human cells, elephant cells demonstrated increased apoptotic response following DNA damage. These findings, if replicated, could represent an evolutionary-based approach for understanding mechanisms related to cancer suppression

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