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Effect of Acid Suppression on Molecular Predictors for Esophageal Cancer

¹ Medical Research Council Cancer Cell Unit, Hutchison-Medical Research Council Research Centre; ² GI Physiology Unit, University College Hospital, London, United Kingdom and ³ Centre for Applied Medical Statistics, Department of Public Health and Primary Care, Institute of Public Health, University Forvie Site, Cambridge, United Kingdom

Requests for reprints: Rebecca C. Fitzgerald, Medical Research Council Cancer Cell Unit, Hutchison-Medical Research Council Research Centre, Hills Road, Cambridge CB2 2XZ, United Kingdom. Phone: 44-1223-763287; Fax: 44-1223-763296. E-mail: rcf{at}hutchison-mrc.cam.ac.uk

Background: Gastroesophageal reflux disease is a risk factor for the development of Barrett's esophagus and esophageal adenocarcinoma. The effect of antireflux therapy on the incidence of esophageal adenocarcinoma is unknown. Acid exposure in vitro induces hyperproliferation via a cyclooxygenase-2 (COX-2) dependent mechanism. Epidemiologic and animal studies suggest that COX inhibitors decrease the incidence of esophageal adenocarcinoma.

Aim: To study the differential effect of complete compared with incomplete acid suppression on proliferation, apoptosis, and COX-2.

Patients and Methods: Fifty-one patients with Barrett's esophagus who underwent pH monitoring were divided into two groups according to their DeMeester score: 32 acid-suppressed patients (group 1) and 19 patients with abnormally high acid exposure (group 2). Slides from biopsies taken 3 months before and 4 and 12 months after pH monitoring were stained for Mcm2, COX-2, c-myc, and cleaved caspase-3 (marker of apoptosis).

Results: There was no evidence of a difference between the two groups in terms of age, gender ratio, medication, dysplasia status, and the expression levels of any marker before pH monitoring. In group 1, Mcm2 expression decreased in the luminal surface and throughout the tissue 12 months after monitoring when compared with the two previous time points (P < 0.05). The levels of COX-2 increased overtime (P < 0.01 in group 1, not significant in group 2). There was no correlation between Mcm2 and COX-2 expression. Acid suppression had no effect on c-myc or apoptosis.

Conclusion: Long-term acid suppression reduces proliferation in Barrett's esophagus samples but has no advantageous effect on c-myc, apoptosis, or COX-2. (Cancer Epidemiol Biomarkers Prev 2006;15(2):288–93)