Scientists have determined why men develop liver cancer at a higher rate than women.Men are four times more likely to develop liver cancer compared to women, due to the sex hormones androgren, the male sex hormone, and estrogen, the female sex hormone.

Researchers at the University of Pennsylvania recently discovered the reason estrogen hormones prevents against liver cancer and androgen hormones increase the risk of liver cancer is due to the proteins the sex hormones bind to. Specifically a group of proteins called Foxa 1 and 2.

Study findings were published in the medical journal Cell.

In past studies, when lab mice were given a liver carcinogen, male mice grew several tumors, while females grew only a small amount, however, these results were reversed when scientists removed the Foxa gene after they induced the mice with cancer, and showed that the actions of both estrogens and androgens in the liver are Foxa dependent, which explains the reversed cancer results among the different gender of mice.

Although results of this experiment were informative, a different approach would be needed by researchers to asses the liver cancer risks among humans, as there are 5,000 different places in the human DNA where Foxa factors can attach themselves.

They looked for specific genetic genetic markers called SNP’s, which is a DNA sequence variation that occurs when a single DNA building block differs amongst members of a biological species, or “paired chromosomes in an individual, according to what the authors wrote.

Since researchers already knew that in women the estrogen receptor protects against liver cancer, they look for SNP markers within Foxa binding sites in tissue samples from those who did and didn’t have liver cancer.

They found that women with liver cancer frequently had SNP’s within specific Foxa binding sites, and proved that mutated SNP acts not only to abolish binding of the Foxa proteins, but also of the estrogen receptor to its main sites, thus decreasing the risk of liver cancer.