Original Contribution
The American Journal of Gastroenterology (2005) 100, 1012–1018; doi:10.1111/j.1572-0241.2005.40904.x
Prediction of Malignant Potential in Reflux Disease: Are Cytokine Polymorphisms Important?
Martin D Gough MB ChB, MRCS (Ed)1, Roger Ackroyd MD, FRCS (Eng Ed)1, Ali W Majeed MD, FRCS (Ed)1 and Nigel C Bird MEd, PhD1
1Academic Surgical Unit, University of Sheffield, Sheffield, United Kingdom
Correspondence: Dr. N.C. Bird, Academic Surgical Unit, K Floor, Royal Hallamshire Hospital, Glossop Rd, Sheffield S10 2JF, UK
Received 3 June 2004; Revised 0000; Accepted 11 November 2004.
Abstract
OBJECTIVES:
Esophageal reflux is common in the Western world and can lead to a number of diseases, such as esophagitis, Barrett's esophagus, and adenocarcinoma. Barrett's predisposes to adenocarcinoma and endoscopic surveillance may lead to earlier detection of adenocarcinoma. However, clinical methods only identify one patient in 15 with Barrett's esophagus. The aim of this study was to find factors that may help identify patients with Barrett's earlier.
METHODS:
Blood samples and detailed histories were taken from 456 patients with gastroesophageal reflux who were recruited into three study groups: esophagitis, Barrett's esophagus without dysplasia, and Barrett's with dysplasia or adenocarcinoma. PCR was used to determine the frequency of five functional cytokine polymorphisms: interleukin-1 receptor antagonist position +2018 (IL-1 Ra +2018), interleukin-1 
position -511 (IL-1 -511), tumor necrosis factor-
position -238 (TNF- -238), interleukin-10 position +1082 (IL-10 +1082), and interleukin-4 receptor position -1902 (IL-4R -1902).
RESULTS:
IL-1 Ra +2018 genotype 2/2 was associated with Barrett's more commonly than esophagitis (OR-3.7, p = 0.0345). The IL-10 +1082 genotype 2/2 was more strongly associated with Barrett's and adenocarcinoma than esophagitis (OR-1.76, p = 0.056 and OR 1.96, p = 0.025, respectively). There were no differences for the IL-1 -511, IL-4R -1902, and TNF- -238 polymorphisms.
CONCLUSIONS:
Cytokine polymorphisms are more commonly found in patients with Barrett's or adenocarcinoma than those with esophagitis. Together with demographic data, this may help identify those patients with Barrett's who would benefit from surveillance.
