title: Androgens and esophageal cancer: What do we know?
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.
authors.affiliation: 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.
authors.forename: Olga A
authors.initials: OA
authors.lastname: Sukocheva
authors.affiliation: 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.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Due
authors.affiliation: 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.
authors.forename: Damian J
authors.initials: DJ
authors.lastname: Hussey
authors.affiliation: 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.
authors.forename: David I
authors.initials: DI
authors.lastname: Watson
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000726:Androgen Antagonists / Q000627:therapeutic use; D000728:Androgens / Q000378:metabolism*; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism; D012307:Risk Factors; D012737:Sex Factors; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C410798:AR protein, human; D000726:Androgen Antagonists; D000728:Androgens; D018931:Antineoplastic Agents, Hormonal; D011944:Receptors, Androgen
keywords: Androgen receptor; Androgens; Esophageal cancer