Distribution and Clinical Impact of Helicobacter pylori Virulence Factors in Epstein-Barr-Virus-Associated Gastric Cancer

Abstract

Background: Helicobacter pylori (HP) and Epstein-Barr virus (EBV) coinfection lead to chronic inflammation and contribute to the development of gastric cancer. However, studies examining the association between HP virulence factors and EBV infection in gastric cancer are limited. This study investigated the polymorphisms of HP virulence factors associated with EBV infection and their effects on clinical outcomes in EBV-associated gastric cancer (EBVaGC). Methods: A total of 96 HP isolates from 54 patients with gastric cancer were divided and analyzed based on EBV coinfection status. Polymerase chain reaction amplifications of virulence factors were conducted using DNA extracts from HP isolates cultured from gastric mucosal specimens. Results: EBV infection was significantly associated with gastric carcinoma with lymphoid stroma morphology and a proximal location in the stomach. Most HP strains from patients with gastric cancer were positive for cagA (100.0%), vacA (100.0%), and iceA1 (87.5%). Among HP isolates with EBV coinfection, the prevalence of iceA2 (21.7% vs. 0.0%, p < 0.001) and ureA (21.7% vs. 4.0%, p = 0.009) was significantly more frequent, and that of iceA1 (78.3% vs. 96.0%, p = 0.009) and vacA s1a (4.3% vs. 22.0%, p = 0.012) was less frequent than those of EBV- colonies. Multivariate analysis indicated that ureA (odds ratio, 6.148; 95% confidence interval [CI], 1.221 to 30.958; p = 0.028) was associated with EBVaGC. No significant difference in clinical outcomes was observed based on the presence of ureA expression in EBVaGC. Conclusions: In gastric cancer, regardless of EBV infection, most HP strains were highly virulent, testing positive for cagA, vacA, and iceA1. Although ureA was significantly associated with EBV infection, it did not influence the clinical outcomes of EBVaGC.

Keywords: Epstein–Barr virus; Helicobacter pylori; stomach neoplasms; virulence factors.

Figure 1

Agarose gel electrophoresis for polymerase chain reaction products of Helicobacter pylori virulence factors in Epstein–Barr-virus-positive colonies. (A) iceA1 (247 bp) (−): 2/3/18/19/23/24/42/43/44/45. (B) ureA (411 bp) (+): 9/10/14/15/18/20/23/30/39/40. DNA size marker: 2000 bp, 1000 bp, 500 bp.