May/June 2008

Liver Cancer and Men

Genes play a big role.

By Sara Shay

Arlin Rogers and his colleagues are looking into why men are likelier than women to develop liver cancer. Credit: Donna Coveney/MIT

Liver cancer kills more than twice as many men as women in the United States every year. MIT researchers have discovered that male genes are partly to blame for the disparity.

Arlin Rogers, chief of comparative pathology at MIT's Division of Comparative Medicine, had theorized that sex hormones influenced the male liver's susceptibility to tumors. In humans, the male liver receives intermittent bursts of growth hormone ­beginning at puberty. The same is true in mice, and male mice also develop liver cancer at higher rates than females.

Rogers and his colleagues infected mice with Helicobacter hepaticus, a bacterium that can cause liver tumors in rodents, much the way hepatitis B and C can in humans. They waited until the infected mice were middle-aged (one year old), because middle age is when liver damage in humans is often first detected. Then they castrated some males and gave others what Rogers calls a "whopping dose" of a powerful male sex hormone. Since previous studies have shown that mice castrated at puberty rarely develop liver cancer, Rogers expected that the castrated mice wouldn't develop tumors and the hormonally charged ones would.

But to Rogers's surprise, neither castration nor supplemental hormones affected the cancer risk of the mature mice. After much genetic analysis, his team discovered that the animals' inflammatory response to infection was what caused cancer. Inflammation disrupted gene expression in the male liver, thus weakening the liver's ability to process toxins and regulate cell growth; inappropriate cell growth can lead to cancer. Female livers are naturally more resistant to inflammation and respond better to it when it occurs.

Rogers hopes his group's findings, recently published in the journal Cancer Research, will speed the discovery of biological targets for new therapies. "Already we have identified potential targets to preserve liver function and hopefully delay or prevent progression to cancer in high-risk patients of both sexes," he says. "This will be the focus of future research in our laboratory and hopefully others."