AIM:To investigate-765G＞C COX-2 polymorphism and H pylori infection in patients with gastric adenocarcinoma,peptic ulcer disease(PUD)and nonulcer dyspepsia(NUD).METHODS:We enrolled 348 adult patients(62 gastric adenocarcinoma,45 PUD and 241 NUD)undergoing upper gastrointestinal endoscopy at two referral centers between September,2002 and May,2007.H pylori infection was diagnosed when any of the four tests (RUT,culture,histopathology and PCR)were positive.Genotyping for-765G＞C polymorphism of COX-2 was performed by PCR-RFLP analysis.RESULTS:Frequency of C carrier had significant association with gastric adenocarcinoma as compared to NUD[77.4%vs 29%,P＜0.001,odds ratio(0R)8.20;95% confidence interval(95%CI),4.08-16.47]and PUD(77.4%vs 31.1%,P＜0.001;OR 8.04;95%CI,3.25-19.90).Risk of gastric adenocarcinoma was significantly higher in patients having C carrier with (OR 7.83;95% CI 3.09-19.85)and without H pylori infection(OR 7.06;95% CI,2.61-19.09).Patients with C carrier and H pylori infection had significant risk for the development of PUD(P＜0.001;OR 5.65;95% CI,2.07-15.34).CONCLUSION:-765G＞C COX-2 polymorphism with or without H pylori could be a marker for genetic susceptibility to gastric adenocarcinoma.COX-2 polymorphism in presence of Hpylori infection might be useful in predictinq the risk of PUD.