Science

Sex hormone explains men's higher liver cancer risk

Last Updated: 2010-05-19 18:35:28 -0400 (Reuters Health)

HONG KONG (Reuters) - Male sex hormones may explain why men with hepatitis B virus (HBV) infection are more likely to develop liver cancer than women, researchers in Taiwan have found.

In a paper published online in Science Translational Medicine on Wednesday, the researchers said hepatitis B viruses attach themselves to androgen receptors before going on to damage liver tissue and cause cancer.

"The findings indicate that using drugs to destroy... androgen receptors could be a new way to battle liver cancer at an early stage," they wrote.

Men are up to seven times more likely than women to develop hepatocellular carcinoma. Among hepatitis B virus carriers, men are up to three times more likely to develop hepatomas than women.

Led by Dr. Ming-Heng Wu at the Institute of Basic Medical Sciences in National Cheng Kung University in Tainan, the researchers found that HBV has a special DNA sequence which draws it to androgen receptors.

"The androgen receptors in liver cells bind to this sequence and trigger a cascade of damage to liver tissue," they said.

In their experiments, they exposed HBV-transgenic mice to the carcinogen N1-N1-diethylnitrosamine.

Some of the mice were genetically modified to be lacking in androgen receptors in their livers.

By week 22 in the experiment, more than 90% of mice with hepatic androgen receptors had developed liver tumors, compared to 27% of the mice without androgen receptors.

The androgen receptor negative mice had a lower incidence of hepatocellular carcinoma, smaller tumor sizes, fewer foci formations, and less alpha-fetoprotein compared to their wild-type littermates.

Blocking the androgen receptors in the liver did not change overall androgen levels or leave any obvious toxic effects in the mice.

"Targeting the androgen receptor rather an androgen could be a promising therapy for liver cancer," the researchers said.

http://stm.sciencemag.org/content/2/32/32ra35.abstract

Science Translational Medicine 2010.