A University of Rochester study helps to explain why men get liver cancer more often than women and opens the door for a new treatment pathway, by showing a direct link between the androgen receptor, which is more active in men, and the hepatitis B virus as it relates to the deadly cancer.
The study is published May 19, 2010, in Science Translational Medicine, a new journal from the American Association for the Advancement of Science, AAAS.
Primary liver cancer is the fifth most common cancer in men. It often arises after infection from the hepatitis B virus (HBV), which is widespread across the globe and growing in the United States. Other studies of liver cancer have focused on risk factors such as age, family history, and use of alcohol and cigarettes, but those epidemiology studies have not explained the mechanisms driving hepatocellular carcinoma and why men are more susceptible.
Now, corresponding author Chawnshang Chang, Ph.D., the George Hoyt Whipple Distinguished Professor of Pathology at the University of Rochester Medical Center, and colleagues, showed that the androgen receptor (AR), a protein that mediates male sex hormones, promotes liver cancer when hepatitis B is present by altering DNA replication of the virus. Chang's laboratory created a mouse model for HBV-induced liver cancer and reported that knocking out AR suppressed the HBV-induced cancer.
According to an accompanying editorial in the journal, the identification of the AR pathway is a potential new treatment target that could translate to the clinic.
"Our study is the first in vivo evidence to demonstrate a direct connection between HBV-induced liver cancer and the AR," Chang said. "This is important because so far most work has focused on eliminating total serum androgen levels, a type of therapy that has shown little success."
"This important paper offers insight into something we have long observed but not entirely understo
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University of Rochester Medical Center