Role of estrogen in liver cancer

Liver cancer is the fifth most common cancer worldwide and despite increasing implementation of ultrasonographic surveillance strategies, its incidence is rising, especially in western countries. A universal characteristic of hepatocellular carcinoma is the striking male prevalence that is found, with few exceptions, both in animals and in humans. Many different hypotheses have been put forward in an attempt to explain this finding, which is not a simple epidemiological oddity but could also have pathogenetic implications. An obvious trail to follow, as gender susceptibility is implicated, is the role played by sex hormones, namely estrogens. Estrogens are not simply involved in reproductive mechanisms; instead, it is increasingly evident that they have a role in such an enormous variety of cellular processes that their implication in liver carcinogenesis may be manifold. The purpose of this review is to provide an overview of the available data, with a special focus on the hormonal mechanisms potentially implicated in the development of liver cancer.