title: Obesity, metabolic syndrome and esophageal adenocarcinoma: epidemiology, etiology and new targets.
abstract: BACKGROUND
  Rates of distal and junctional adenocarcinomas are increasing in Western countries.
  
  
  METHODS
  Systematic review of epidemiological evidence linking obesity to esophageal adenocarcinoma (EA) was performed for studies published from 2005 to 2010. The current understanding of obesity's role in the etiology and potential dysplastic progression of Barrett's esophagus (BE) to EA is reviewed.
  
  
  RESULTS
  Accumulating epidemiological studies provide evidence of obesity's role as a driving force behind the increasing rates of EA. The simplest construct is that obesity promotes reflux, causing chronic inflammation and BE, predisposing to adenocarcinoma. However, as obesity is positively associated with the prevalence of many cancers, other mechanisms are important. A link may exist between fat distribution patterns and the risk of BE and EA. Altered metabolic profiles in the metabolic syndrome (MetS) may be a key factor in cell cycle/genetic abnormalities that mark the progression of BE towards cancer. Research highlighting a unique role of MetS in the length of BE, and its association with systemic inflammation and insulin resistance is discussed, as well as adipokine receptor expression in both BE and esophageal epithelium, and how MetS and the systemic response impacts on key regulators of inflammation and tumorigenesis. CONCLUSIONS/IMPACT: Obesity is positively associated with EA. The systemic inflammatory state consequent on the altered metabolism of obese patients, and the associated impact of adipocytokines and pro-coagulant factors released by adipocytes in central fat, may underlie obesity's relationship to this cancer. Novel therapeutic agents that may antagonize adipo-cytokines and potentially offer a promising role in cancer therapy are discussed.
authors.affiliation: Department of Nutrition, Food Studies & Public Health, New York University, New York, NY 10044, USA. aoife.ryan1@gmail.com
authors.forename: Aoife M
authors.initials: AM
authors.lastname: Ryan
authors.forename: Michelle
authors.initials: M
authors.lastname: Duong
authors.forename: Laura
authors.initials: L
authors.lastname: Healy
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Ryan
authors.forename: Niyati
authors.initials: N
authors.lastname: Parekh
authors.forename: John V
authors.initials: JV
authors.lastname: Reynolds
authors.forename: Derek G
authors.initials: DG
authors.lastname: Power
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology* / Q000209:etiology; D015331:Cohort Studies; D004938:Esophageal Neoplasms / Q000453:epidemiology* / Q000209:etiology; D006801:Humans; D024821:Metabolic Syndrome / Q000453:epidemiology* / Q000209:etiology; D009765:Obesity / Q000453:epidemiology* / Q000209:etiology; D011446:Prospective Studies