Helicobacter pylori infection in relation to E-cadherin gene promoter polymorphism and hypermethylation in sporadic gastric carcinomas

AIM: To study Helicobacter pylori (H pylori) infection in relation to E-cadherin (E-cad) promoter polymorphism and hypermethylation in GCs. METHODS: Specimens were taken from representative cancerous lesions and adjacent non-cancerous epithelia of 67 resected GCs. H pylori was detected by real-time PCR of the cagA gene from non-neoplastic epithelium. E-cad promoter polymorphism and hypermethylation were determined by restriction fragment length polymorphism analysis and methylation-specific PCR, respectively. Expression of E-cad protein was determined by immunohistochemistry. RESULTS: H pylori was found in 57% of patients with GC. H pylori infection was more frequently found in tumors with the -160C/C genotype than those with the -160C/A and -160A/A genotypes (74% vs 47%, P = 0.02). H pylori infection was associated with E-cad methylation in nonneoplastic epithelium; however, no significant difference in H pylori was observed between methylated and unmethylated cancerous lesions. CONCLUSION: Patients with the -160C/C genotype might require H pylori infection to promote the inactivation of CDH1, suggesting that H pylori infection might affect GC in an initial stage because polymorphism is germ line. Mechanism of hypermethylation of CDH1 promoter in GC is complex, and H pylori infection might affect it in an initial stage. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.