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Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans

Overview of attention for article published in JAMA: Journal of the American Medical Association, November 2015
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (99th percentile)
  • High Attention Score compared to outputs of the same age and source (99th percentile)

Citations

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183 Dimensions

Readers on

mendeley
423 Mendeley
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1 CiteULike
Title
Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans
Published in
JAMA: Journal of the American Medical Association, November 2015
DOI 10.1001/jama.2015.13134
Pubmed ID
Authors

Lisa M. Abegglen, Aleah F. Caulin, Ashley Chan, Kristy Lee, Rosann Robinson, Michael S. Campbell, Wendy K. Kiso, Dennis L. Schmitt, Peter J. Waddell, Srividya Bhaskara, Shane T. Jensen, Carlo C. Maley, Joshua D. Schiffman

Abstract

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). 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. 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). 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.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 423 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 6 1%
Japan 6 1%
United Kingdom 4 <1%
Canada 3 <1%
Netherlands 2 <1%
Brazil 1 <1%
Finland 1 <1%
Ireland 1 <1%
France 1 <1%
Other 1 <1%
Unknown 397 94%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 81 19%
Student > Ph. D. Student 79 19%
Researcher 75 18%
Student > Master 36 9%
Other 33 8%
Other 83 20%
Unknown 36 9%
Readers by discipline Count As %
Agricultural and Biological Sciences 140 33%
Biochemistry, Genetics and Molecular Biology 109 26%
Medicine and Dentistry 54 13%
Immunology and Microbiology 11 3%
Veterinary Science and Veterinary Medicine 9 2%
Other 45 11%
Unknown 55 13%

Attention Score in Context

This research output has an Altmetric Attention Score of 1775. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 July 2020.
All research outputs
#1,923
of 15,575,554 outputs
Outputs from JAMA: Journal of the American Medical Association
#86
of 27,861 outputs
Outputs of similar age
#19
of 254,225 outputs
Outputs of similar age from JAMA: Journal of the American Medical Association
#1
of 405 outputs
Altmetric has tracked 15,575,554 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 99th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 27,861 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 58.6. This one has done particularly well, scoring higher than 99% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 254,225 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 99% of its contemporaries.
We're also able to compare this research output to 405 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 99% of its contemporaries.