AIM:To investigate the interrelationship of Epstein-Barrvirus(EBV)and EBV-encoded proteins with Helicobacterpylori(H pylori)infection and the expression of c-metand c-myc oncogene proteins in gastric carcinoma,andto explore their role in gastric carcinogenesis.METHODS:One hundred and eighty-five gastriccarcinoma tissues were detected by polymerase chainreaction(PCR)-Southern blot for EBV genome and insitu hybridization(ISH)for EBV-encoded small RNA1(EBER1).Gastric carcinoma with positive EBER1signals was confirmed EBV-associated gastric carcinoma(EBVaGC).The status of H pylori infection in 185 gastriccarcinomas was assessed by rapid urease test and PCR.The samples with positive PCR and urease test weredefined as H pylori infection.The expression of c-metand c-myc oncogene proteins in tissues of EBVaGC andmatched EBV-negative gastric carcinoma(EBVnGC)were examined by immunohistochemistry.RT-PCRand Southern hybridization were used to detect theexpression of nuclear antigens(EBNAs)1 and 2,latentmembrane protein(LMP)1,early genes BARF1 andBHRF1 in EBVaGC cases.RESULTS:The positive rate of H pylori and EBV in185 gastric carcinomas was 59.45%(110/185)and7.03%(13/185)respectively.No difference was foundin sex,age,pathological differentiation,clinical stagesand lymph node metastasis between H pylori-positiveand H pylori-negative gastric carcinomas.However,thepositive rate of H pylori infection in the antrum gastric carcinomas was higher than that of cardia and bodygastric carcinomas.In our series,age,pathologicaldifferentiation,clinical stages,lymph node metastasisand location of cancer were not different betweenEBVnGC and EBVaGC,while the positive rate of EBV inmale patients was significantly higher than that of femalepatients.The positivity of H pylori in EBV-associated andEBV-negative gastric carcinomas was 46.15%(6/13)and81.40%(104/172)respectively.There was no significantcorrelation between EBV and H pylori infection.Thec-met overexpression was significantly higher in theEBVaGC group than in the EBVnGC group.However,c-met and c-myc expression did not show significantdifference between the two groups.Transcripts of EBNA1were detected in all 13 EBVaGCs,while both EBNA2and LMP1 mRNA were not detected.Six of the 13 casesexhibited BARF1 transcripts and 2 exhibited BHRF1transcripts.CONCLUSION:The positivity of H pylori in EBVnGCsis higher than that of EBVaGCs,but no significantcorrelation is found between EBV infection and Hpylori infection.H pylori-positive gastric carcinoma ispredominant in antrum location,while EBVaGC hasa tendency of predominance in cardia/body location.EBV infection is associated with c-met abnormalexpression but not with c-myc protein in EBVaGC.c-metoverexpression is not induced by LMP1.BARF1 andBHRF1 may play important roles in the tumorigenesis ofEBVaGC through different pathways.