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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 28, 2015; 21(20): 6146-6156
Published online May 28, 2015. doi: 10.3748/wjg.v21.i20.6146
Androgens and esophageal cancer: What do we know?
Olga A Sukocheva, Bin Li, Steven L Due, Damian J Hussey, David I Watson
Olga A Sukocheva, Bin Li, Steven L Due, Damian J Hussey, David I Watson, Flinders University Department of Surgery, Flinders Medical Centre, Adelaide, South Australia 5042, Australia
Author contributions: Sukocheva OA and Li B wrote the first draft; Due SL, Hussey DJ and Watson DI critically reviewed and edited the paper; all authors contributed to design and structure of the paper.
Conflict-of-interest: The authors declare no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: David I Watson, Professor, Head, Flinders University Department of Surgery, Flinders Medical Centre, Room 3D211, Bedford Park, South Australia 5042, Australia. david.watson@flinders.edu.au
Telephone: +61-8-82046086 Fax: +61-8-82046130
Received: January 23, 2015
Peer-review started: January 24, 2015
First decision: March 10, 2015
Revised: March 27, 2015
Accepted: April 16, 2015
Article in press: April 17, 2015
Published online: May 28, 2015
Processing time: 127 Days and 2.9 Hours
Abstract

Significant disparities exist between genders for the development and progression of several gastro-intestinal (GI) diseases including cancer. Differences in incidence between men vs women for colon, gastric and hepatocellular cancers suggest a role for steroid sex hormones in regulation of GI carcinogenesis. Involvement of intrinsic gender-linked mechanisms is also possible for esophageal adenocarcinoma as its incidence is disproportionally high among men. However, the cause of the observed gender differences and the potential role of androgens in esophageal carcinogenesis remains unclear, even though the cancer-promoting role of androgen receptors (AR) shown in other cancers such as prostate and bladder suggests this aspect warrants exploration. Several studies have demonstrated expression of ARs in esophageal cancer. However, only one study has suggested a potential link between AR signaling and outcome - poorer prognosis. Two groups have analyzed data from cohorts with prostate cancer and one of these found a decreased incidence of esophageal squamous and adenocarcinoma after androgen deprivation therapy. However, very limited information is available about the effects of androgen and AR-initiated signaling on esophageal cancer cell growth in vitro and in vivo. Possible mechanisms for androgens/AR involvement in the regulation of esophageal cancer growth are considered, and the potential use of AR as a prognostic factor and clinical target is highlighted, although insufficient evidence is available to support clinical trials of novel therapies. As esophageal adenocarcinoma is a gender linked cancer with a large male predominance further studies are warranted to clarify the role of androgens and ARs in shaping intracellular signaling and genomic responses in esophageal cancer.

Keywords: Esophageal cancer; Androgens; Androgen receptor

Core tip: Esophageal cancers, especially adenocarcinoma, are gender-linked malignancies, with a male predominance. Previous studies have demonstrated expression of androgen receptors in both adenocarcinoma and squamous cell esophageal cancer. However, the impact of androgens in development and progression of these cancers is unclear. Androgen-deprivation therapy has not been explored, even though it is successfully used in treatment of prostate cancers. Further studies are warranted to clarify the role of androgens and androgen receptors in shaping intracellular signaling and genomic responses in esophageal cancer.