Liver fluke infection is a major public health problem affecting more than 10 million people in Southeast Asia, particularly in Thailand and Laos. Infection has been strongly linked to cholangiocarcinoma, or bile duct cancer, an uncommon but aggressive form of cancer.
This particular cancer is caused by the chronic infection with a parasitic worm acquired by consuming uncooked or undercooked freshwater fish. The population in Thailand impacted by the infection, routinely prepares and consumes undercooked fish caught by locals to lower costs.
A team led by Paul Brindley, PhD, professor of microbiology, immunology, and tropical medicine at the George Washington University School of Medicine and Health Sciences, has received more than $1.7 million from the National Cancer Institute at the National Institutes of Health to investigate the cellular and molecular links between liver fluke infection and bile duct cancer.
"We are trying to figure out why this worm infection causes these liver cells to transform and become cancer," said Brindley. "It's an infection-related cancer and we're intrigued by and motivated to resolve the basic cellular question of how could a worm induce human tissue in the liver to become malignant."
Brindley also explained that while cholangiocarcinoma is most prevalent in Southeast Asia, it is not exclusive to the region. There have been reports of the cancer in the United States and areas of the West, including in military veterans who had been stationed in Southeast Asia.
The risk factors that explain why people get cholangiocarcinoma in the West are less clear, given that the parasitic worm does not occur in these regions. Brindley and his team anticipate that their research can provide insight and a biomarker in the local people that would allow researchers to take an easier tissue sample, like blood or urine, and try to detect the change that liver fluke causes to make the cancer occur.
Through gene editing, the team has already mutated one gene from the worm that makes the worm less virulent and are characterizing other parasite genes that contribute to the malignant changes in the human bile duct liver cells.
"Lots of people die from this infection. It's a global public health problem – a neglected tropical disease that we would like to control," Brindley said.