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

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.