Genetic flaw triggers liver cancer, diabetes in males

When researchers altered the NCOA5 gene in male mice, "ninety-four percent of the male mice we looked at developed the liver cancer, while 100 percent of these mice developed glucose intolerance," says Hua Xiao. (Credit: Robynlou Kavanagh/Flickr)

A genetic deficiency in males can set off the development of one of the most common types of liver cancer and forms of diabetes, according to research with mice.

The new study, published in the journal Cancer Cell, shows that when the NCOA5 gene, present in both men and women, is altered to a deficient level in male mice, a spontaneous reaction occurs that produces cells that can lead to hepatocellular carcinoma. The type of liver cancer is two-to-four times more prevalent in men than women.


The findings also show that prior to cancer development there are occurrences of glucose intolerance, a prediabetic condition that is believed to increase the risk of type 2 diabetes in humans. Female mice did not develop these diseases.

“Essentially, what this provides is evidence for a genetic susceptibility in males to this particular type of liver cancer and diabetes,” says Hua Xiao, lead researcher of the project and associate professor of physiology at Michigan State University.

“Ninety-four percent of the male mice we looked at developed the liver cancer, while 100 percent of these mice developed glucose intolerance.”

The reason for the distinct outcomes between males and females may also have to do with the different levels of hormones between genders.

Estrogen protection

“Because estrogen may function through the NCOA5 gene and previously has been found to play somewhat of a protective role against both diseases, the result is a decreased risk in females,” Xiao says. “Since males produce lower amounts of estrogen, this can contribute to their susceptibility.”

Type 2 diabetes has been widely associated with liver cancer as a common risk factor. Yet due to the increasing prevalence of diabetes worldwide and the limited treatments for hepatocellular carcinoma, this research could open the door to new therapeutic options.

“At this point, it’s not known if the genetic deficiency can be reversed and needs to be investigated further,” Xiao says. “But if it can somehow be changed through treatments such as drug therapies, this could substantially increase the chances of men in particular warding off these diseases.”

The National Institute of Health funded the research.

Source: Michigan State University