Prediction of malignant potential in reflux disease: are cytokine polymorphisms important?
OBJECTIVE
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 beta position -511 (IL-1 beta-511), tumor necrosis factor-alpha position -238 (TNF-alpha-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 beta-511, IL-4R -1902, and TNF-alpha-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.
Gough
Martin D
MD
Academic Surgical Unit, University of Sheffield, Sheffield, United Kingdom.
Ackroyd
Roger
R
Majeed
Ali W
AW
Bird
Nigel C
NC
D000230:Adenocarcinoma / Q000209:etiology / Q000276:immunology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000209:etiology / Q000276:immunology; D004938:Esophageal Neoplasms / Q000209:etiology* / Q000276:immunology; D004942:Esophagitis, Peptic / Q000209:etiology / Q000276:immunology; D005260:Female; D005544:Forecasting; D005764:Gastroesophageal Reflux / Q000150:complications* / Q000276:immunology; D005838:Genotype; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D019948:Receptors, Interleukin-4 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D007375:Interleukin-1; D007378:Interleukins; D017472:Receptors, Interleukin-1; D019948:Receptors, Interleukin-4; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10