Raw Fish Spread Liver Cancer

Uncooked fish can cause human liver cancer, but most sushi lovers need not worry since the condition comes only from eating certain freshwater fish.

The human liver fluke, a freshwater parasite endemic to areas of Thailand, Japan, and Siberia, triggers human liver cancer by creating harmful cell mutations, encouraging tumor growth, and stopping normal cell death, according to a study released yesterday in the journal PLoS Pathogens.

The research could help prevent millions of people from developing liver cancer.

The International Agency for Research on Cancer "has classified Opisthorchis viverrini as a Class One carcinogen," said Sutas Suttiprapa, a scientist at George Washington University and a co-author of the PLoS Pathogens papers.

"I think that over the next year or next few years there will be a big campaign to treat and give these people some knowledge to stop eating raw fish."

There are actually three species of microscopic human liver fluke. O. viverrini is endemic to streams and lakes in Thailand, Laos, and Cambodia and was the actual species of fluke tested by the scientists. Another fluke lives in Siberia, and yet another is found in Japan and Korea.The parasite is only found in freshwater however, so eating sushi from the ocean is safe to eat.

Like many parasites, the human liver fluke has a complicated life span. An egg is first released from the human host. A snail eats the egg, which hatches and begins to develop.

Eventually a free swimming larvae emerges from the snail and attaches to the skin of a freshwater fish. When a human eats the fish raw, or as most people in Thailand are infected, by eating a delicacy of fermented fish, the parasite emerges from the small intestine and takes up residence inside the liver.

Once in the liver three things happen that eventually lead to cancer. First, the body tries to kill the fluke by producing free oxygen radicals. The fluke is largely immune from these attacks, however, so the radicals rebound, enter the body's own liver cells, and mutate human DNA.

Next, the fluke inadvertently encourages these mutated cells reproduce. Granulin, a growth factor, helps the fluke reproduce. Unfortunately for humans, granulin also encourages human cancer cells to reproduce and grow.

Finally, the flukes prevent the cancer cells from dying at their appointed time. Apoptosis, or programmed cell death, is one way the body stops cancer cells from developing. The flukes produce another protein that stops apoptosis, according to unpublished results.

Just having the fluke along creates a small number of liver cancers, but diet accounts for most liver cancers in infected patients. The popular fermented fish delicacy, known locally as plaa raa, contains large amounts of nitrosamines, another carcinogen linked to prostate cancer.

"In early studies hamsters were infected with the liver fluke along, and a small number of hamsters developed cancer," said Suttiprapa. "But when they put nitrosamines in with the liver fluke, they found that most hamsters developed the cancer."

The human liver fluke is not the only pathogen linked to cancer. Helicobacter pylori, herpes, and other microorganisms cause cancer in less than one percent of the infected population. Of the roughly nine million people infected with Opisthorchis viverrini, an estimated 33 percent will develop liver cancer.

There is hope for people infected with the flatworm. The parasite can, and often is, killed with praziquantel, one of the WHO's Essential Medicines. The problem is that people take a cavalier approach to infection.

"They can take the medicine to cure themselves of the fluke," said Suttiprapa. "But every reinfection causes more and more damage to the bile ducts."

Linking a parasite to a cancer is very rare, says Polly Sager, a scientist at the National Institute of Allergy and Infectious Diseases familiar with the research. Linking consumption of raw fish to cancer should help reduce the prevalence of liver cancer in areas of Thailand, Laos, and neighboring countries. It also gives cancer researchers here in the US another way to study another path to cancer.

"This could be a mechanism that is used in other types of cancer," said Sager. "Anytime we can figure out any mechanism for how something heads down the path to cancer is a good thing to know because we can look for it in other cancers."