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Elephants’ tumour suppressing gene TP53 could help stamp out cancer

LONDON — Elephants may hold the key to fighting cancer after scientists found that they carry a large number of genes that suppress tumours.

LONDON — Elephants may hold the key to fighting cancer after scientists found that they carry a large number of genes that suppress tumours.

Researchers have long puzzled over why elephants rarely develop cancer, even though they have life-spans that are similar to humans, living for about 70 years.

Now a team at the University of Chicago has found that the pachyderms carry 20 copies of a tumour suppressing gene called TP53. Most other species, including humans, only carry one set.

The scientists found that the extra copies of the gene heightened sensitivity to DNA damage, which causes the cells to quickly commit suicide when damaged, before they can go on to reproduce and form deadly tumours.

The study also found that when the same genes were activated in mice, they developed the same cancer resistance as elephants, suggesting that the method could be used to block the spread of cancer.

Study author Dr Vincent Lynch said: “A major constraint on the evolution of large body sizes in animals is an increased risk of developing cancer.

“If all cells have a similar risk of malignant transformation an organism with many cells should have a higher risk of developing cancer than organisms with fewer cells

“Organisms with long lifespans have more time to accumulate cancer-causing mutations than organisms with shorter lifespans and therefore should be at an increased risk of developing cancer.”

However scientists discovered that elephants were not at an increased risk of cancer, in a discovery dubbed “Peto’s Paradox” named after Oxford University scientist Sir Richard Peto, who found that the incidence of cancer does not correlate with the number of cells in an organism.

Large creatures with long lifespans, such as elephants and whales, did not have more chance of developing cancer and, in fact, seemed to be less likely to die of the disease. Even moderately sized animals, such as roe deer, are at a lower risk, with just 2 per cent of the population dying from cancer.

Now scientists believe they know why. Elephants are the first species found to have 20 copies of a gene that stops cancer growth by spotting when the DNA cells are damaged and preventing them from replicating.

The researchers suggest that this mutation may have allowed larger animals to evolve without suffering the ravages of cancer, which should have coincided with large growth.

“These results suggest that an increase in the copy number of TP53 may have played a direct role in the evolution of very large body sizes,” said Dr Lynch. “These changes apparently evolved without major life-history trade-offs, such as shortened lifespan, accelerated ageing, or reduced fertility. It may be possible to develop a drug that mimics the function of the TP53 gene. The next steps are to figure out precisely how these extra copies are working in the cell, and if there are other genes with elephant-specific changes evolved in their cancer resistance.”

The researchers hope it may now be possible to use this newly discovered protein to develop new treatments that can help stop cancers from spreading or even developing in the first place.

The only other creature that seems to have a similar genetic protection against cancer is the naked mole rat. Earlier this year, the University of Rochester in New York discovered the creatures have a cluster of genes that produce four proteins responsible for preventing damaged cells that might cause cancer from multiplying and so prevent tumours from growing.

The University of Chicago team also showed that while woolly mammoths had the same genetic protection, mastodons did not, suggesting that could be one reason the huge ice age creatures died out. The research was published on the online science network BioRxiv. THE DAILY TELEGRAPH

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