Solving a Massive Mystery

All things being equal, large animals should have the highest risk of cancer. The more cells a body has, the more opportunity there is for cancerous mutations to arise.

Why, then, does cancer rarely afflict elephants?

A recent study provides answers to this sizable mystery, revealing that elephants possess extra copies of a wide variety of genes associated with tumor suppression. Understanding how they got this way, say researchers, could potentially lead to new ways of treating cancer.

Study co-author Vincent Lynch, associate professor of biology at the University at Buffalo, calls the existence of large, cancer-resistant animals “a long-standing paradox in evolutionary medicine and cancer biology, [one that] indicates that evolution found a way to reduce cancer risk.”

According to Lynch, past research already has looked at TP53, a well-known tumor suppressor. “This time, we said, ‘Let’s just look at whether the entire elephant genome includes more copies of tumor suppressors than what you’d expect.’ Is the trend general? Or is the trend specific to one gene?”

They learned it was the former. “Elephants have lots and lots and lots of extra copies of tumor-suppressor genes, and they all contribute probably a little bit to cancer resistance.”

The researchers found that many relatives of the elephant harbor extra copies of tumor-suppressor genes, but elephant genomes possess some unique duplications. These duplications may be contributing to tumor suppression through genes involved in DNA repair, resistance to oxidative stress, and cellular growth, aging and death.

“By determining how big, long-lived species evolved better ways to suppress cancer, we can learn something new about how evolution works,” says co-author Juan Manuel Vazquez, a postdoctoral researcher at UC Berkeley. And that, adds Lynch, could lead to “new and innovative ways to prevent and treat cancer.”