Inflammatory Protein may be why Liver Cancer is More Prevalent in Men than Women

Michael Karin, Ph.D.
University of California San Diego
P42ES010337, R37ES004151, and R01ES006376

A study in mice carried out by NIEHS grantees at the University of California San Diego may shed light on why the most common form of liver cancer strikes men with three to five times the frequency as women. Hepatocellular carcinoma is fairly rare in the U.S.; however it is the fifth most common cancer worldwide. It arises from a variety of causes including viral hepatitis infection, chronic alcoholism, and exposure to aflatoxin or a combination of these factors.

The research team led by Dr. Michael Karin, treated mice with the potent liver carcinogen diethyl nitrosamine. All of the male mice developed liver tumors, but only 10-20 percent of the female mice. Further investigation showed that the male mice produced much more of the inflammatory protein interleukin-6 (IL6) than the females. Additional experiments determined that when IL6 was eliminated in the male mice, the liver cancer rate dropped by about 90 percent bringing it in line with the rate in the female mice. Treating the male mice with estrogen also lowered IL6 production and reduced liver disease to the same level as the female mice.

The researchers postulate that similar mechanisms may be responsible for the different rates of liver cancer in men and women. They suggest that reducing IL6 levels in men, interfering with the protein’s action, or administering estrogen-like compounds to reduce IL6 production may offer new liver cancer treatment options. This discovery may have implications for bladder cancer, which also occurs more frequently in men.

Citation: Naugler WE, Sakurai T, Kim S, Maeda S, Kim K, Elsharkawy AM, Karin M. Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science. 2007 Jul 6;317(5834):121-4.