Bile Duct Cancer From Liver Fluke Infection

Roxanne Nelson

June 23, 2011

June 23, 2011 — Infection with the parasitic liver fluke Opisthorchis viverrini does not always lead to bile duct cancer, but nearly all cases of cholangiocarcinoma develop in individuals with this infection. Hence, the liver flukes are officially classified by the World Health Organization as Group 1 carcinogens.

This link between the cancer and the infection is now being investigated at the George Washington University School of Medicine and Health Sciences, which has just been awarded a 5-year, $500,000-per-year grant from the National Cancer Institute. The grant will support research into the development of proteomic biomarkers for O viverrini–induced cholangiocarcinoma.

This is a rare cancer, explained reward recipient Jeffrey M. Bethony, PhD, associate professor of microbiology, immunology, and tropical medicine. "Only a very small percentage of people infected with the liver fluke will develop the cancer, but nearly all cancers develop in persons who are infected."

Opisthorchis viverrini

The global "epicenter" of cholangiocarcinoma is the region along the Chi River basin in Northeast Thailand, where infection with O viverrini is endemic. The parasite is also endemic in Laos, Vietnam, and Cambodia, but it is difficult study cancer incidence in those countries. "They have a less developed infrastructure, and probably do not have tissue registries," Dr. Bethony told Medscape Medical News. "We also have to look at the demographics; the people generally don't live as long and they need to be chronically infected for many years before cancer develops."

O viverrini is a food-borne parasite that is believed to infect more than 40 million people, primarily in Southeast Asia. Raw fish is the immediate host for the parasite and is a staple of the diet in that region, Dr. Bethony explained.

"It would be very difficult to get them to change their eating habits," he said. "This is a poor region and food sources are limited. The majority of people living here have all been infected."

The prevalence of human infection can be as high as 70% in some regions, such as the Khon Kaen Province in Thailand, Dr. Bethony noted. Even though the parasite can be effectively treated with the anthelmintic drug praziquantel, people tend to be reinfected because of their continued consumption of raw fish.

Bile duct cancer is associated with a late presentation, and there is no effective chemotherapy to treat the disease. Therefore, in addition to intervention strategies that focus on preventing or treating liver fluke infection, there is a need to identify biomarkers than can be measured early and in accessible samples, he explained.

Dr. Bethony and his colleagues will use a quantitative proteomics approach to scan tumor tissues and matched plasma patients with cholangiocarcinoma to identify a suite of candidate biomarkers proximal to the disease site. Any potential biomarkers identified during the analysis of tumor tissue will be verified in the plasma of healthy individuals who are at risk for bile duct cancer from O viverrini infection. These individuals are all enrolled in the Khon Kaen Cholangiocarcinoma Cohort study, which was established by Dr. Bethony and Paul J. Brindley, PhD, professor of microbiology, immunology, and tropical medicine, as part of an International Collaboration in Infectious Disease Research grant that was awarded from the National Institute of Allergy and Infectious Diseases.

"This is a very good model to use to study cancer," said Dr. Bethony. "We know who to follow, we can identify a large group of people who are at risk for developing cancer, and we can follow them over time."

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