Gut doi:10.1136/gutjnl-2011-300653
  • Oesophagus
  • Original article

Serum ghrelin is inversely associated with risk of subsequent oesophageal squamous cell carcinoma

  1. Neal D Freedman1
  1. 1Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
  2. 2Department of Public Health Analysis, School of Community Health and Policy, Morgan State University, Baltimore, Maryland, USA
  3. 3Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, California, USA
  4. 4Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
  1. Correspondence to Dr Gwen Murphy, Nutritional Epidemiology Branch, DCEG, National Cancer Institute, 6120 Executive Blvd., EPS 3034, Rockville, MD 20892, USA; murphygw{at}
  1. Contributors GM: conducted all analysis and wrote the manuscript. FK, SMD, CCA and NDF: were involved in the planning and execution of analysis and advised on the manuscript. FZS: oversaw the laboratory analysis and advised on manuscript preparation. JV: advised on planning and execution of the study with respect to the ATBC study and advised on manuscript preparation. SJW, PRT and DA: advised on the planning of the study, analysis and manuscript preparation.

  • Revised 7 November 2011
  • Accepted 10 November 2011
  • Published Online First 16 December 2011


Background Gastric atrophy, as determined by a low serum pepsinogen I:II ratio, may be associated with an increased risk of oesophageal squamous cell carcinoma (OSCC). Ghrelin, a hormone which, is also produced in the gastric fundic glands may be a marker of gastric atrophy, but its association with OSCC is not known.

Methods To examine the relationship between baseline serum ghrelin concentration and subsequent risk of OSCC, the authors conducted a nested case–control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study. 82 cases of OSCC were matched (1:1) by age and date of blood draw to controls from the ATBC study. Serum ghrelin was measured by radioimmunoassay. ORs and 95% CIs were calculated using conditional logistic regression with adjustment for potential confounders.

Results For individuals in the lowest quartile of serum ghrelin, compared to those in the highest, the multivariate OR of subsequent OSCC was 6.83 (95% CI 1.46 to 31.84). These associations were dose dependent (p value for trend =0.005 for both), and independent of the effects of low pepsinogen I:II ratio and Helicobacter pylori infection. The significance of these associations remained even for individuals developing OSCC up to 10 years after baseline ghrelin measurement, although they become attenuated after 10 years.

Conclusion Lower baseline concentrations of serum ghrelin were associated with an increase in risk of OSCC. Further studies are needed to confirm this finding in other populations and to explore the role of ghrelin in the aetiology of OSCC.


  • Funding Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study was supported by funding provided by the Intramural Research Program of the National Cancer Institute and US Public Health Service contracts (N01-CN-45165, N01-RC-45035, N01-RC-37004).

  • Competing interests None.

  • Ethics approval Ethics approval was provided by the National Cancer Institute USA and the National Public Health Institute, Finland.

  • Provenance and peer review Not commissioned; externally peer reviewed.