Helicobacter pyloriCagA Seropositivity and Gastric Carcinoma Risk in a Japanese American Population

Abstract

Helicobacter pylori colonization is associated with gastric cancer, but whether and to what extent the risk is greater for strains with the cagA gene than for those without needs to be determined. Between 1967 and 1977, 9963 Japanese American men were recruited and examined. By 1996, incident cases of gastric carcinoma of the distal stomach had been diagnosed in 261 men. Stored serum samples from these case patients and 261 age-matched control subjects were tested for immunoglobulin G antibodies to H. pylori and to the CagA product of H. pylori, using antibody-specific enzyme-linked immunosorbent assays. Compared with H. pylori-negative, CagA-negative men, H. pylori-positive, CagA-negative men had an odds ratio (OR) of 2.7 (95% confidence interval [CI], 1.3-5.6) for intestinal gastric carcinoma. Men seropositive for both H. pylori and CagA had an OR of 4.1 (95% CI, 2.2-7.7). This suggests that colonization by an H. pylori strain with the cagA gene is associated with a greater risk of intestinal gastric carcinoma.

Helicobacter pylori Stimulates Gastric Epithelial Cell MMP-1 Secretion via CagA-dependent and -independent ERK Activation

“…pylori gastric colonization stimulates inflammatory, erosive, and neoplastic processes (62). That H. pylori strains lacking cagA induce less inflammation (63), and are less commonly associated with both peptic ulceration, (19,64) and gastric adenocarcinoma (18,64), suggests that inflammation and these processes may be linked. Although the mechanisms by which H. pylori induces ulceration are not well understood, the ability of H. pylori to stimulate gastric cell secretion of various MMPs (24 -26, 65-68) suggests that H. pylori induces stromal destruction and host cell de-adherence via MMP-mediated degradation of collagens and other connective tissue proteins.…”

“…Other cagA and/or cagI-related effects include increased host cell apoptosis (14), nuclear factor-B activation (15), and secretion of pro-inflammatory chemokines such as interleukin-6 and -8 (16,17). Compared with cagA Ϫ strains, cagA ϩ strains are associated with increased risk of peptic ulcer disease and carcinogenesis (18,19).…”

Low-Positive Antibody Titer againstHelicobacter pyloriCytotoxin-Associated Gene A (CagA) May Predict Future Gastric Cancer Better Than Simple Seropositivity againstH. pyloriCagA or againstH. pylori

“…However, it has not been elucidated whether the magnitude of immune response to CagA is associated with risk for gastric cancer. Thus far, only one study investigated the association between CagA antibody titer and gastric cancer in a prospective way (16) and another study investigated the issue in a retrospective way (17). Interestingly, a low titer of CagA IgG antibody was associated with high risk for gastric cancer in both studies, although it was not clear whether the observed phenomenon was reproducible in other prospective and retrospective studies.…”

Helicobacter pylori CagA Phosphorylation Status Determines the gp130-activated SHP2/ERK and JAK/STAT Signal Transduction Pathways in Gastric Epithelial Cells

“…Helicobacter pylori frequently colonizes the human stomach (1), and hosts infected by cagA-positive strains are at increased risk of gastric cancer and peptic ulceration (2)(3)(4)(5)(6)(7)(8)(9)(10). H. pylori injects the CagA protein into host gastric epithelial cells via a type IV secretion system (11)(12)(13)(14)(15)(16).…”