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World J Gastroenterol. Sep 7, 2014; 20(33): 11496-11504
Published online Sep 7, 2014. doi: 10.3748/wjg.v20.i33.11496
Ulcerative colitis: From inflammation to cancer. Do estrogen receptors have a role?
Mariabeatrice Principi, Michele Barone, Maria Pricci, Nicola De Tullio, Giuseppe Losurdo, Enzo Ierardi, Alfredo Di Leo
Mariabeatrice Principi, Maria Pricci, Nicola De Tullio, Giuseppe Losurdo, Enzo Ierardi, Alfredo Di Leo, Division of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy
Michele Barone, Division of Gastroenterology, Department of Medical and Surgical Sciences, University of Foggia, 71100 Foggia, Italy
Author contributions: Principi M, Barone M, Ierardi E and Di Leo A, designed the study, revised the manuscript and approved the final version; Pricci M, De Tullio N and Losurdo G collected the data and revised the final version before approval.
Correspondence to: Enzo Ierardi, MD, Adjunct Professor, Associate Professor, Senior Scientist, Division of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Piazza Umberto I, 70124 Bari, Italy.
Telephone: +39-80-5592577 Fax: +39-80-5593088
Received: February 20, 2014
Revised: March 29, 2014
Accepted: May 23, 2014
Published online: September 7, 2014

Ulcerative colitis (UC) is a condition at increased risk for colorectal carcinoma (CRC) development. Nowadays, screening and follow-up programs are routinely performed worldwide to promote the early detection of CRCs in subjects with well known risk factors (extent, duration and severity of the disorder). The diffusion of these procedures is presumably the main reason for the marked reduction of cancer incidence and mortality in the course of UC. In addition, chemoprevention has been widely investigated and developed in many medical fields, and aspirin has shown a preventive effect against CRC, while mesalazine has been strongly invoked as a potential chemopreventive agent in UC. However, available studies show some limitations due to the obvious ethical implications of drug withdrawal in UC in order to design a control group. The estrogen receptors (ER) alpha/beta balance seems to have a relevant influence on colorectal carcinogenesis and ER beta appears to parallel apoptosis, and hence an anti-carcinogenic effect. Phytoestrogens are compounds acting as ER beta agonists and have shown a promising chemopreventive effect on sporadic as well as genetically inherited CRC. There is evidence suggesting a role for ERs in UC-related carcinogenesis. In this perspective, since these substances can be considered as dietary supplements and are completely free from side effects, phytoestrogens could be an interesting option for CRC prevention, even when the disease is a consequence of long-term chronic inflammation, as in the course of UC. Further studies of their effects are warranted in both the basic research and clinical fields.

Keywords: Ulcerative colitis, Epithelial dysplasia, Colorectal cancer, Estrogen receptors, Chemoprevention, Phytoestrogens, Dietary supplementation, Inflammatory bowel disease

Core tip: The present work outlines the main data regarding a possible involvement of estrogen receptors in colorectal carcinogenesis, paying particular attention to cancer arising in the course of ulcerative colitis. A protective role for beta receptors has been suggested by many studies. The challenge for the future could be to devise chemopreventive strategies against colorectal carcinoma employing estrogen receptor beta agonists, such as phytoestrogens.