Gender differences in liver cancer risk explained

Men are four times more likely to develop liver cancer than women, a difference attributed to the sex hormones androgen and estrogen, but the molecular mechanisms by which estrogens prevent -- and androgens promote -- liver cancer has remained unclear. Now, new research from the University of Pennsylvania has found that the difference depends on which proteins the sex hormones bind next to, specifically a group of transcriptional regulatory proteins called Foxa 1 and 2. Normally, when mice are given a liver carcinogen, male mice develop many tumors while females get very few. Strikingly, this gender-related incidence of liver cancer was completely reversed in mice genetically engineered by the team to lack the Foxa genes. Using complex genomic analyses, the researchers could show that the actions of both estrogens and androgens in the liver are Foxa dependent, explaining the reversal in cancer risk.