Estrogen Receptors in Colorectal Cancer: Facts, Novelties and Perspectives

Colorectal cancer (CRC) is the second cause of cancer-related death in both sexes worldwide. As pre-menopausal women are less likely to develop CRC compared to age-matched men, a protective role for estrogens has been hypothesized. Indeed, two isoforms of nuclear estrogen receptors (ER) have been described: ER alpha and ER beta. While the binding of 17beta-estradiol to ER alpha activates anti-apoptotic pathways, the interaction with ER beta activates caspase-3, inducing apoptosis. In this regard, several pieces of evidence show that ER beta tends to be under-regulated in advanced adenomas and CRC, with an opposite trend for ER alpha. Furthermore, ER beta stimulation slows adenomatous polyp growth and modulates relevant CRC pathways. Based on such considerations, dietary modulation of ER is promising, particularly in subjects with genetic predisposition for CRC. Nevertheless, the main limitation is the lack of clinical trials on a large population scale.