Researchers from The George Washington University School of Medicine and Health Sciences (SMHS) have been awarded a five-year, $500,000-per-year R01 grant from the National Cancer Institute (NCI) of the National Institutes of Health (NIH). This award will support investigations by SMHS researchers who are developing proteomic biomarkers for Opisthorchis-induced bile duct cancer. The liver fluke Opisthorchis viverrini is a food-borne parasite that currently infects more than 40 million people, primarily in the Southeast Asian countries of Thailand, Laos, and Cambodia, where uncooked fish, intermediate hosts for O. viverrini, are a staple of the diet. O. viverrini is considered among the most important of the food-borne trematodes due to its strong association with bile duct fibrosis and bile duct cancer (cholangiocarcinoma) as determined by the World Health Organization's International Agency for Research on Cancer (IARC). IARC categorizes this parasitic worm as a Group 1 carcinogen – a definitive cause of cancer.
With this award, Jeffrey M. Bethony, Ph.D., Associate Professor of Microbiology, Immunology, and Tropical Medicine, and Paul J. Brindley, Ph.D., Professor of Microbiology, Immunology, and Tropical Medicine at GW's SMHS will use a quantitative proteomics approach to scan tumor tissues and matched plasma from bile duct cancer patients to identify a suite of candidate biomarkers proximal to the disease site. Potential biomarkers identified during the analysis of tumor tissue will be verified in the plasma of healthy individuals at risk of bile duct cancer from O. viverrini infection who are enrolled in the Khon Kaen (Thailand) Cholangiocarcinoma Cohort study, established by Drs. Brindley and Bethony as part of an International Collaboration in Infectious Disease Research (ICIDR) grant awarded from the National Institute of Allergy and Infectious Diseases (NIH). The cohort recruits residents in O. viverrini endemic areas along the Chi River basin in Northeastern Thailand (Isaan), the global epicenter of cholangiocarcinoma, and is currently following over 1,000 individuals identified to be at high risk of developing liver fluke-induced bile duct cancer.
"Cholangiocarcinoma is associated with a late presentation", said Dr. Brindley, "and, therefore, poses great challenges for diagnosis and has a high mortality rate. These features highlight the need for biomarkers than can be measured early and in accessible samples, such as plasma."
This project will be undertaken in cooperation with Dr. Banchob Sripa, head of the Tropical Disease Research Laboratory, Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand and Drs. Jason Mulvenna and Alexander Loukas, Queensland Tropical Health Alliance, James Cook University, Cairns, Australia.
"O. viverrini induced bile duct cancer provides a unique model of human carcinogenesis, with the major risk factor and many of the intermediate stages on the pathway to cancer already well-defined," Dr. Bethony said, "This enables us to track the presence of biomarkers from the initiation of cancer risk to culmination in bile duct cancer."
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