Leptin and the risk of Barrett's oesophagus

Bradley J Kendall ¹, Graeme A Macdonald ², Nicholas K Hayward ¹, John B Prins ², Ian Brown ³, Neal Walker ⁴, Nirmala Pandeya ¹, Adele C Green ¹, Penelope M Webb ¹ and David C Whiteman ^1*

¹ QIMR, Australia
² University of Queensland, Australia
³ Sullivan and Nicolaides Pathology, Australia
⁴ Queensland Medical Laboratories, Australia

^* To whom correspondence should be addressed. E-mail: david.whiteman{at}qimr.edu.au.

Accepted 1 December 2007

Abstract

Background: Obesity is associated with increased risks of Barrett’s oesophagus (BO) and oesophageal adenocarcinoma (OA). Alterations in serum leptin and adiponectin, obesity-related cytokines, have been linked with several cancers, and have been postulated as potential mediators of obesity-related carcinogenesis, however the relationship with BO remains unexplored.

Methods: We measured serum leptin and adiponectin concentrations on two subsets of participants within a case-control study conducted in Brisbane, Australia. Cases were people aged 18-79 years with histologically confirmed BO newly diagnosed between 2003-2006. Population controls, frequency matched by age and sex to cases, were randomly selected from the electoral roll. Phenotype and medical history data were collected through structured, self-completed questionnaires. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression analysis.

Results: In the pilot analysis (51 cases, 67 controls) risks of BO were highest among those in the highest quartile of serum leptin (OR 4.6, 95% CI 0.6-33.4). No association was seen with adiponectin. In the leptin validation study (306 cases, 309 controls), there was a significant three-fold increased risk of BO among males in the highest quartile of serum leptin (OR 3.3, 95% CI 1.7-6.6) and this persisted after further adjustment for symptoms of gastro-oesophageal reflux (OR 2.4, 95% CI 1.1-5.2). In contrast, the risk of BO among females decreased with increasing serum leptin concentrations.

Conclusions: High serum leptin is associated with increased risk of BO among males but not females. This association is not explained simply by higher body mass or gastro-oesophageal reflux among cases. The mechanism remains to be determined.

Keywords: Barrett's oesophagus, Oesophageal cancer, case-control study, obesity, risk factors

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