Gene Linking Hepatitis B and Liver Cancer Identified

City of Hope
Tuesday, 10 June 2003

Liver Cancer Is Now the Leading Cause of Cancer Death in Asia

Researchers at City of Hope Cancer Center have identified a gene specifically involved in the progression of hepatitis B infection to liver cancer.

"This gene is a very good marker for the diagnosis of liver cancer and may be a target for future therapies to prevent hepatitis patients from developing liver cancer," said Yun Yen, M.D., of City of Hope's division of Medical Oncology and Therapeutic Research and chief investigator of the study, which appears in the current issue of American Journal of Pathology.

Hepatitis B has long been recognized as a major risk factor for liver cancer. Of the nearly 150,000 people in the U.S. each year who contract the virus, 15-20 percent subsequently develop liver cancer. In China and East Asia, where hepatitis B is endemic, liver cancer is the leading cause of cancer death.

But until now, the genetic steps that lead from infection by the hepatitis B virus to cancer were unknown.

Using microarray technology, the researchers compared genetic activity in two groups of hepatitis B patients—those with liver cancer and those without the disease. Of the thousands of genes screened, researchers found that one was under expressed, or "switched off," in hepatitis B patients with liver cancer. The gene cannot be identified by name because it could be patented.

"It is a member of a family of genes responsible for repairing damage from different toxins and infections to our genetic material, but it has not been well characterized," said Dr. Yen.

The researchers also found that unlike some other well-known cancer genes, the under expression of this gene is unique to liver cancer.

"New diagnostic tests based on the gene could potentially detect liver cancer at an early stage and help doctors determine which hepatitis patients are at risk for developing cancer so they can be surveilled more closely," said Donald David, M.D., director of the department of Gastroenterology at City of Hope and co-author of the study.

Currently, many cancers are discovered only when they become symptomatic and have progressed too far to be treated effectively. Fatigue is the only outward symptom of hepatitis B. Liver cancer usually produces no symptoms until its advanced stage.

In a second avenue of research, said Dr. David, "we are looking at drugs that could potentially boost expression of the gene, restore the repair process and stave off the progression of cancer."

The research team included Weihua Qiu, Ph.D.; Dr. Donald David; Bingsen Zhou, Ph.D.; Peiguoi G. Chu, Ph.D., all of City of Hope; Bohe Zhang, Ph.D., and Mengchao Wu, Ph.D.; Jiacheng Xiao, Ph.D.; Tianquan Han, Ph.D.; Zenggang Zhu, Ph.D.; Taingxiang Wang, P.h.D.; Xiyong Liu, Ph.D., all of Eastern Hepatobilary Surgery Hospital, Shanghai, China; Richard Lopez, Ph.D., St. Vincent Hospital, Los Angeles; Paul Frankel, Ph.D., and Ambrose Jong, Ph.D., both of the University of Southern California, Los Angeles.

The research was funded with a grant from the Ralph M. Parsons Foundation.

For more information, or to contact City of Hope, see their website at: www.cityofhope.org