Aflatoxin-induced genetic mutations could help catch liver cancer early

Aflatoxins are produced by molds that can grow on crops, such as maize. Image: Sam Fentress/CC BY-SA 2.0

An MIT team has identified a set of mutations in liver cells that could help catch exposure to aflatoxins, which are thought to cause liver cancer, before tumors develop.

Aflatoxins are poisonous chemicals produced by certain fungi that grow on crops, such as grains, peanuts and tree nuts. Exposure to aflatoxins is associated with a higher risk of liver cancer, according to the National Cancer Institute. Previous research by senior author John Essigmann suggested that exposure triggers a genetic mutation that can often lead to liver cancer.

In the new study, published in the Proceedings of the National Academy of Sciences, the researchers exposed mice to aflatoxins within a few days of birth. All of the mice eventually developed liver tumors, they said in a statement.

The team sequenced the mice’s DNA at the 10-week mark—before tumors developed—and DNA from the tumors. At 10 weeks, they found a “distinctive pattern of mutations” that could work as a marker for aflatoxin exposure.

“What we’re doing is creating a fingerprint,” said Essigmann, a professor of of biological engineering and chemistry at MIT, in the statement. “It’s really a measure of prior exposure to something that causes cancer.”

“It’s very early-onset, and you don’t see it with other carcinogens, to our knowledge,” he said.

The team studied the genetic sequences of liver tumors from more than 300 patients. The “fingerprint” in the mouse models resembled the signatures of 13 patients, who were thought to have been exposed to aflatoxins, according to the statement.

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Catching liver cancer early is difficult, because symptoms often don’t show up until the disease is in later stages, the American Cancer Society said. The five-year survival rate for a patient with localized liver cancer is 31% and the rate drops to 3% for patients whose cancer has metastasized.

A number of companies are working on liquid biopsies, or blood tests that catch cancer early. Grail is using “ultradeep sequencing” to create a test that spots tiny bits of tumor DNA that circulate in a patient’s bloodstream, thereby detecting cancer in its earliest—and most treatable—stages.

While the MIT team used DNA sequencing in their work, the researchers hope to develop a simpler test that could identify patients who have been exposed to aflatoxins, but haven’t developed tumors yet, and would benefit from regular liver cancer screening. They also plan to investigate other mutational profiles brought about by other carcinogens.