Association of insulin and insulin-like growth factors with Barrett's oesophagus
- Katarina B Greer1,
- Cheryl L Thompson2,
- Lacie Brenner1,
- Beth Bednarchik1,
- Dawn Dawson3,
- Joseph Willis3,
- William M Grady5,
- Gary W Falk4,
- Gregory S Cooper1,
- Li Li2,
- Amitabh Chak1
- 1Division of Gastroenterology and Liver Disease, University Hospitals Case Medical Center, Cleveland, Ohio, USA
- 2Family Medicine, Case Western Reserve University, University Hospitals Case Medical Center, Cleveland, Ohio, USA
- 3Department of Pathology, University Hospitals Case Medical Center, Cleveland, Ohio, USA
- 4Department of Gastroenterology and Hepatology, Cleveland Clinic Foundation, Cleveland, Ohio, USA
- 5Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
- Correspondence to Dr Katarina B Greer, 11100 Euclid Ave, WRN 5066, Cleveland, OH 44106, USA; katkagreer{at}yahoo.com
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Contributors AC, LL, GSC, WMG, DD and JW were responsible for the study design. GWF was responsible for recruitment of patients at the Cleveland Clinic site. BB and LB were responsible for data collection and patient enrollment. KBG and CLT were responsible for data analysis. AC is the principal investigator. All authors participated equally in the preparation of the manuscript.
- Revised 3 August 2011
- Accepted 4 August 2011
- Published Online First 19 September 2011
Abstract
Background It is postulated that high serum levels of insulin and insulin growth factor 1 (IGF-1) mediate obesity-associated carcinogenesis. The relationship of insulin, IGF-1 and IGF binding proteins (IGFBP) with Barrett's oesophagus (BO) has not been well examined.
Methods Serum levels of insulin and IGFBPs in patients with BO were compared with two separate control groups: subjects with gastro-oesophageal reflux disease (GORD) and screening colonoscopy controls. Fasting insulin, IGF-1 and IGFBPs were assayed in the serum of BO cases (n=135), GORD (n=135) and screening colonoscopy (n=932) controls recruited prospectively at two academic hospitals. Logistic regression was used to estimate the risk of BO.
Results Patients in the highest tertile of serum insulin levels had an increased risk of BO compared with colonoscopy controls (adjusted OR 2.02, 95% CI 1.15 to 3.54) but not compared with GORD controls (adjusted OR 1.55, 95% CI 0.76 to 3.15). Serum IGF-1 levels in the highest tertile were associated with an increased risk of BO (adjusted OR 4.05, 95% CI 2.01 to 8.17) compared with the screening colonoscopy control group but were not significantly different from the GORD control group (adjusted OR 0.57, 95% CI 0.27 to 1.17). IGFBP-1 levels in the highest tertile were inversely associated with a risk of BO in comparison with the screening colonoscopy controls (adjusted OR 0.11, 95% CI 0.05 to 0.24) but were not significantly different from the GORD control group (adjusted OR 1.04, 95% CI 0.49 to 2.16). IGFBP-3 levels in the highest tertile were inversely associated with the risk of BO compared with the GORD controls (OR 0.36, 95% CI 0.16 to 0.81) and also when compared with the colonoscopy controls (OR 0.40, 95% CI 0.20 to 0.79).
Conclusions These results provide support for the hypothesis that the insulin/IGF signalling pathways have a role in the development of BO.
- Insulin
- insulin growth factors
- central adiposity
- Barrett's oesophagus
- Barrett's carcinoma
- Barrett's metaplasia
- epidemiology
- growth factors
- gastrointestinal pathology
- Barretts metaplasia
- Barretts carcinoma
- Barretts oesophagus
- colorectal neoplasia
- colon carcinogenesis
- mucosal pathology
- pancreatic pathology
- colorectal pathology
- histopathology
- colorectal cancer genes
- microsatellite instability
- cell cycle
- gastrointestinal neoplasia
- molecular pathology
- gastro-oesophageal reflux disease
- Barretts metaplasia
- Barretts carcinoma
- Barretts oesophagus
- dysplasia
- oesophageal cancer
- non-cardiac chest pain
- diagnostic and therapeutic endoscopy
- dysphagia
- oesophageal disorders
- cancer prevention
- cancer epidemiology
Footnotes
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Funding This research was supported by grant R21 CA135692 from the National Cancer Institute. AC is supported by grant K24 DK002800 from the National Institute of Diabetes and Digestive and Kidney Diseases.
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Competing interests None.
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Patient consent Obtained.
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Ethics approval This study was conducted with the approval of the Institutional Review Board of the Case Comprehensive Cancer Center.
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Provenance and peer review Not commissioned; externally peer reviewed.
