Role of the insulin-like growth factor 1 axis and visceral adiposity in oesophageal adenocarcinoma

Br J Surg. 2012 Mar;99(3):387-96. doi: 10.1002/bjs.8658. Epub 2012 Jan 12.

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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Body Mass Index
  • Enzyme-Linked Immunosorbent Assay
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism*
  • Intra-Abdominal Fat / metabolism*
  • Intra-Abdominal Fat / pathology
  • Male
  • Middle Aged
  • Obesity, Abdominal / metabolism
  • Obesity, Abdominal / pathology
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / metabolism
  • Survival Analysis
  • Waist Circumference

Substances

  • RNA, Messenger
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1