Detection of oxidative DNA damage in oesophageal biopsies of patients with reflux symptoms and normal pH monitoring

Background: Gastro-oesophageal reflux has been shown to induce oxidative DNA damage. Aim: To determine whether oxidative DNA damage, detected in oesophageal biopsies by simple immunohistochemical staining, correlates with gastro-oesophageal reflux disease as determined by pH monitoring. Methods: The study included 47 patients with reflux symptoms who had oesophageal biopsy and 24-h pH monitoring studies performed within 3 months of each other with no variation in treatment in the time between the two procedures. Sections of formalin-fixed and paraffin-embedded oesophageal biopsies were stained for 8-hydroxy-2'-deoxyguanosine using the standard immunoperoxidase method. Positive nuclear immunoreactivity was considered to indicate oxidative DNA damage. Results: Seven (33%) of the 21 cases with normal 24-h pH monitoring results were negative for oxidative DNA damage, compared with only two (8%) of the 26 cases with abnormal 24-h pH results (P = 0.058, two-sided Fisher's exact test). Five of the patients with normal 24- h pH results had oesophageal biopsies performed within 24 h of the monitoring procedure and, of these, four (80%) were positive for oxidative DNA damage, including a case in which both biopsy and 24- h pH monitoring were performed on the same day whilst the patient was on proton pump inhibitor therapy. All cases with normal 24- h pH results and positive oxidative DNA damage showed features of reflux on routine morphological evaluation. Conclusions: Oxidative DNA damage can occur in the absence of acid reflux and despite adequate antisecretory therapy. This may indicate that other agents, such as bile, can induce oxidative DNA damage in an acid-suppressed environment. The significant discordance between oxidative DNA damage and 24- h pH results makes the determination of oxidative DNA damage a poor surrogate marker for 24- h pH monitoring.