Low-positive antibody titer against Helicobacter pylori cytotoxin-associated gene A (CagA) may predict future gastric cancer better than simple seropositivity against H. pylori CagA or against H. pylori.
ABSTRACT To investigate the IgG antibody titer against Helicobacter pylori CagA as a risk factor for future noncardia gastric cancer.
A nested case-control study was done in the longitudinal cohort of atomic bomb survivors using stored sera before diagnosis (mean, 2.3 years). Enrolled were 299 cancer cases and 3 controls per case selected from cohort members matched on age, gender, city, and time and type of serum storage and countermatched on radiation dose.
H. pylori IgG seropositive with CagA IgG low titer was the strongest risk factor for noncardia gastric cancer [relative risk (RR), 3.9; 95% confidence interval (95% CI), 2.1-7.0; P < 0.001], especially for intestinal-type tumor (RR, 9.9, 95% CI, 3.5-27.4; P < 0.001), compared with other risk factors, H. pylori IgG seropositive with CagA IgG negative (RR, 2.2; 95% CI, 1.3-3.9; P = 0.0052), H. pylori IgG seropositive with CagA IgG high titer (RR, 2.0; 95% CI, 1.3-3.2; P = 0.0022), chronic atrophic gastritis (RR, 2.4; 95% CI, 1.8-3.3; P < 0.001), current smoking (RR, 2.3; 95% CI, 1.4-3.5; P < 0.001), or radiation dose (RR, 2.1; 95% CI, 1.2-3.1; P = 0.00193). Current smoking showed significantly higher risk for diffuse-type than intestinal-type tumors (P = 0.0372). Radiation risk was significant only for nonsmokers, all noncardia, and diffuse-type gastric cancers.
A low CagA IgG titer is a useful biomarker to identify a high-risk group and it also provides a clue to understanding host-pathogen interaction.
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ABSTRACT: Subjects infected with H. pylori containing cagA do not always induce serum CagA antibody. Our previous meta-analysis showed that serum CagA seropositivity was associated with gastric cancer even in East Asian countries. However, it remains unclear why serum CagA positive status is associated with gastric cancer. In this study, we aimed to examine the relationship between anti CagA antibody titer and the levels of pepsinogen, and histological score. Eighty-eight H. pylori positive Japanese patients with gastritis were included. Serum CagA antibody titer, pepsinogen (PG) I and PG II were evaluated by enzyme-linked immunosorbent assay. Histological scores were evaluated according to Update Sydney System. CagA expression was examined by immunoblot. Seroprevalence of CagA antibody was found in 75.0%. Interestingly, serum CagA antibody titer was significantly correlated with PG I and PG II levels (P = 0.003 and 0.004, respectively). Serum CagA antibody titer was also significantly correlated with mucosal inflammation in the corpus (P = 0.04). On the other hand, bacterial density was not related with CagA antibody titer. CagA expression level of the strains was irrespective of the status of PG and serum CagA antibody. Subjects with higher serum CagA antibody titer can be considered as high risk population for the development of gastric cancer from the point of strong gastric inflammatory response even in Japan. Host recognition rather than bacterial colonization might be associated with the difference of serum CagA antibody titer.Journal of Gastroenterology and Hepatology 08/2013; · 3.33 Impact Factor
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ABSTRACT: Gastric cancer (GC) is a highly malignant cancer with increasing incidence and mortality worldwide. Serum Helicobacter pylori CagA antibody has been widely reported to play an important role in diagnosing GC. However, published data on this subject are inconclusive. Therefore, we performed a meta-analysis to evaluate the sensitivity and specificity of serum H. pylori CagA antibody in the diagnosis of GC. We conducted a comprehensive search to identify eligible related studies, in which the pooled sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curves could be determined. A total of 12 studies including 1,524 cases and 3,324 controls who fulfilled all of the inclusion criteria were included for analysis. The summary estimates for serum H. pylori CagA antibody in the diagnosis of GC in these studies were pooled sensitivity 0.71 (95 % CI 0.69-0.73), specificity 0.40 (95 % CI 0.39-0.42), DOR 2.11 (95 % CI 1.55-2.8), and the area under the curve was 0.636. Our meta-analysis showed that serum H. pylori CagA antibody should not be used for detecting GC.Tumor Biology 08/2014; · 2.84 Impact Factor
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ABSTRACT: Helicobacter pylori (H. pylori) is a flagellated, spiral-shaped, microaerophilic Gram-negative bacillus that colonises the gastric mucosa of more than 50% of the human population. Infection is a risk factor for gastritis, ulcer disease and stomach cancer. Immunity against H. pylori is mainly related to Th1/Th17 skewing, and the activation of regulatory T cells is the main strategy used to limit inflammatory responses, which can result in the pathogen persistence and can lead to chronic gastrointestinal diseases, including cancer. Furthermore, host genetic factors that affect cytokines may determine differences in the susceptibility to many diseases. In this review, we present the cytokine profiles and the main cytokine gene polymorphisms associated with resistance/susceptibility to H. pylori and discuss how such polymorphisms may influence infection/disease outcomes.World Journal of Gastroenterology 05/2014; 20(18):5235-5243. · 2.43 Impact Factor