title: Role of the insulin-like growth factor 1 axis and visceral adiposity in oesophageal adenocarcinoma.
abstract: BACKGROUND
  Epidemiological studies have linked obesity with many cancers. The insulin-like growth factor (IGF) 1 axis may be an important mediator in obesity-associated cancer. This study examined the relationship between IGF-1 and its receptor (IGF-1R) in oesophageal adenocarcinoma, a cancer strongly linked to obesity.
  
  
  METHODS
  Patients with oesophageal adenocarcinoma considered suitable for attempted curative treatment were studied. Visceral adiposity was defined by waist circumference or visceral fat area. Free and total IGF-1 in serum were measured by enzyme-linked immunosorbent assay. Quantitative polymerase chain resection was used to determine mRNA expression of IGF-1 and IGF-1R in resected tumour samples. IGF-1R expression in tissue microarrays (TMAs) was quantified by immunohistochemistry.
  
  
  RESULTS
  A total of 220 patients were studied. Total and free IGF-1 levels were significantly increased in the serum of viscerally obese patients. Gene expression analysis revealed a significant association between obesity status and both IGF-1R (P = 0·021) and IGF-1 (P = 0·031) in tumours. TMA analysis demonstrated that IGF-1R expression in resected tumours was significantly higher in viscerally obese patients than in those of normal weight (P = 0·023). Disease-specific survival was longer in patients with negative IGF-1R expression than in those with IGF-1R-positive tumours (median 60·0 versus 23·4 months; P = 0·027).
  
  
  CONCLUSIONS
  This study highlighted the association of the IGF axis with visceral obesity, and a potential impact on the biology of oesophageal adenocarcinoma through its receptor. Targeting the IGF axis may have a rationale in future studies.
authors.affiliation: Department of Surgery, Trinity Centre for Health Sciences, Trinity College Dublin/St James's Hospital, Dublin, Ireland.
authors.forename: C L
authors.initials: CL
authors.lastname: Donohoe
authors.forename: S L
authors.initials: SL
authors.lastname: Doyle
authors.forename: S
authors.initials: S
authors.lastname: McGarrigle
authors.forename: M C
authors.initials: MC
authors.lastname: Cathcart
authors.forename: E
authors.initials: E
authors.lastname: Daly
authors.forename: A
authors.initials: A
authors.lastname: O'Grady
authors.forename: J
authors.initials: J
authors.lastname: Lysaght
authors.forename: G P
authors.initials: GP
authors.lastname: Pidgeon
authors.forename: J V
authors.initials: JV
authors.lastname: Reynolds
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D004797:Enzyme-Linked Immunosorbent Assay; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D050152:Intra-Abdominal Fat / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D055105:Waist Circumference
chemical_list: D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1