Increased acid exposure in patients with gastroesophageal reflux disease influences cyclooxygenase-2 gene expression in the squamous epithelium of the lower esophagus.
OBJECTIVE
Although genetic changes associated with the progression to Barrett esophagus and adenocarcinoma have been identified, changes in gene expression associated with gastroesophageal reflux disease have not been reported. We examined expression levels of several genes important in carcinogenesis and compared expression levels with alterations in esophageal acid exposure.


METHODS
Prospective analysis of 61 patients initially seen with reflux symptoms at a private academic hospital.


METHODS
Paired esophageal biopsy specimens of squamous epithelium 3 cm above the squamocolumnar junction. All patients had 24-hour pH monitoring performed.


METHODS
Cyclooxygenase (COX) 1, COX-2, thymidylate synthase, human telomerase reverse transcriptase (hTERT), Bcl-2 protein, survivin protein, secreted protein acidic and rich in cysteine (SPARC), tetraspan (TSPAN), and caudal-type homeobox transcription factor 2 (CDX2) messenger RNA expression analysis was performed on snap-frozen, microdissected tissue using a quantitative reverse transcriptase-polymerase chain reaction method. Linear regression and the Pearson product moment correlation were used to relate gene expression to parameters of the 24-hour pH record.


RESULTS
Expression levels of COX-2 correlated positively with the 24-hour pH score (r = 0.25, P =.05). There was no correlation between the expression of other tested genes and esophageal acid exposure. There was also no significant increase in COX-2 expression in patients with esophagitis or in those who used nonsteroidal anti-inflammatory drugs.


CONCLUSIONS
To our knowledge, these data provide among the first reported correlation of genetic changes and increased esophageal acid exposure in patients with gastroesophageal reflux symptoms. The changes in gene expression occur before any metaplastic changes in the tissue are apparent, and may in the future be useful in predicting which patients will progress through a metaplasia-dysplasia carcinoma sequence.
Hamoui
Nahid
N
Department of Surgery, Division of Thoracic and Foregut Surgery, University of Southern California, Los Angeles 90033, USA.
Peters
Jeffrey H
JH
Schneider
Sylke
S
Uchida
Kazumi
K
Yang
Dongyun
D
Vallböhmer
Daniel
D
Valboehmer
Daniel
D
Hagen
Jeffrey A
JA
DeMeester
Steven R
SR
DeMeester
Tom R
TR
Danenberg
Kathleen
K
Danenberg
Peter
P
D000328:Adult; D000368:Aged; D001471:Barrett Esophagus / Q000201:enzymology / Q000473:pathology; D051546:Cyclooxygenase 2; D018450:Disease Progression; D004947:Esophagus / Q000201:enzymology* / Q000473:pathology; D005260:Female; D005764:Gastroesophageal Reflux / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008679:Metaplasia / Q000201:enzymology; D008875:Middle Aged; D011446:Prospective Studies; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases