The incidence of gastric cancer in Okinawa is lowest in Japan. Some previous reports using small number of strains suggested that the high prevalence of Helicobacter pylori with Western-type cagA in Okinawa compared to other areas in Japan might contribute to the low incidence of gastric cancer. It has still not been confirmed why the prevalence of Western-type cagA strains is high in Okinawa. We examined the association between the virulence factors of H. pylori and gastroduodenal diseases in Okinawa. The genotypes of cagA and vacA of 337 H. pylori strains were determined by PCR and gene sequencing.

BackgroundIn 2005, the first disease-specific Helicobacter pylori virulence factor that induced duodenal ulcer and had a suppressive action on gastric cancer has been identified, and was named duodenal ulcer promoting gene (dupA). However, the importance of the dupA gene on clinical outcomes is conflicting in subsequent studies. The aim of this study was to estimate the magnitude of the risk for clinical outcomes associated with dupA gene.MethodsA meta-analysis of case-control studies which provided raw data on the infection rates with the dupA-positive H. pylori detected by polymerase chain reaction was performed.ResultsSeventeen studies with a total of 2,466 patients were identified in the search. Infection with the dupA-positive H. pylori increased the risk for duodenal ulcer by 1.41-fold (95% confidence interval [CI], 1.12-1.76) overall. Subgroup analysis showed that the summary odds ratio (OR) was 1.57 (95% CI, 1.19-2.06) in Asian countries and 1.09 (95% CI, 0.73-1.62) in Western countries. There was no association between the presence of the dupA gene and gastric cancer and gastric ulcer. Publication bias did not exist.ConclusionOur meta-analysis confirmed the importance of the presence of the dupA gene for duodenal ulcer, especially in Asian countries.

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Aims-In east-Asian countries, while almost all Helicobacter pylori strains possess the cytotokine-associated gene A (CagA) gene, serum CagA antibody is not detected in some infected subjects. We aimed to clarify the association between anti-CagA antibody and gastric cancer in east-Asian countries.Materials & methods-We performed a meta-analysis of case-control studies with age-and sex-matched controls, which provided raw data in east-Asian countries.Results-Ten studies with a total of 4325 patients were identified in the search. Some reports from Japan, Korea and China showed a positive association between the presence of anti-CagA antibody and gastric cancer; however, the results differed in their various backgrounds. The disparate findings appeared to result from the use of different methods or from variations in the antigens used to detect the anti-CagA antibody. CagA seropositivity was associated with an increased risk of developing gastric cancer. Conclusion Financial & competing interests disclosureThis report is based on work supported in part by grants from the National Institutes of Health DK62813 and by Ministry of Education, Science, Sports and Culture of Japan; Grant numbers 22390085 and 22659087. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. . This suggests that serum CagA antibody may be a more useful marker in east-Asian countries than the cagA gene. In this study, we performed a meta-analysis for the relationship between anti-CagA antibody and gastric cancer in east-Asian countries. NIH Public Access Materials & methodsA literature search was performed using the PubMed database for articles published from January 1990 to March 2010, using the following words: 'CagA', 'enzyme linked immunosorbent assay (ELISA)' or 'serological' or 'seropositive' or 'seropositivity' or 'serum antibody', and 'Japan' or 'China' or 'Korea' or 'east Asia'. Inclusion criteriaThe following criteria were applied to select fully published case-control studies examining the relationship between anti-CagA antibody of H. pylori and gastric cancer in adult populations: healthy controls were matched with cases by age and sex; the presence of antiCagA antibody was examined by ELISA, immunoblot or both, and all original articles were published in English. H. pylori status was examined serologically by ELISA or immunoblot. Studies were excluded if raw data were not presented, or a histological diagnosis of gastric cancer was not confirmed. When it appeared that the same subjects were presented in multiple reports, the earliest paper was selected. All potentially relevant articles were reviewed by two investigators (Seiji Shiota and Yoshio Yamaoka) independently and disagreement was resolved by discussion. Data extractionData were extracted from each ...

BackgroundAlthough the iceA (induced by contact with epithelium) allelic types of Helicobacter pylori have been reported to be associated with peptic ulcer, the importance of iceA on clinical outcomes based on subsequent studies is controversial. The aim of this study was to estimate the magnitude of the risk for clinical outcomes associated with iceA.MethodsA literature search was performed using the PubMed and EMBASE databases for articles published through April 2011. Published case-control studies examining the relationship between iceA and clinical outcomes (gastritis, peptic ulcer, including gastric ulcer and duodenal ulcer, and gastric cancer) were included.ResultsFifty studies with a total of 5,357 patients were identified in the search. Infection with iceA1-positive H. pylori increased the overall risk for peptic ulcer by 1.26-fold (95% confidence interval [CI], 1.09–1.45). However, the test for heterogeneity was significant among these studies. Sensitivity analysis showed that the presence of iceA1 was significantly associated with peptic ulcer (odds ratio [OR] = 1.25, 95% CI = 1.08–1.44). The presence of iceA2 was inversely associated with peptic ulcer (OR = 0.76, 95% CI = 0.65–0.89). The presence of iceA was not associated with gastric cancer. Most studies examined the cagA status; however, only 15 studies examined the correlation and only 2 showed a positive correlation between the presence of cagA and iceA1.ConclusionOur meta-analysis confirmed the importance of the presence of iceA for peptic ulcer, although the significance was marginal.

Background Helicobacter pylori dupA can be divided into two types according to the presence or absence of the mutation. In addition, full-sequenced data revealed that dupA has two types with different lengths depend on the presence of approximately 600 bp in the putative 5' region (presence; long-type and absence; short-type), which has not been taken into account in previous studies. Methods A total of 319 strains isolated from Okinawa, the south islands of Japan, were included. The status of dupA and cagA was determined by polymerase chain reaction. The presence of mutations in long-type dupA was determined by DNA sequencing. Results The prevalence of long-type dupA was 26.3% (84/319). Sequence analysis showed that there were only 6 cases (7.1%) with point mutations lead to stop codon among 84 long-type dupA strains studied. Interestingly, intact long-type dupA without frameshift mutation, but not short-type dupA was significantly associated with gastric ulcer and gastric cancer than gastritis (P = 0.001 and P = 0.019, respectively). After adjustment by age, gender and cagA, the presence of intact long-type dupA was significantly associated with gastric ulcer and gastric cancer compared with gastritis (odds ratio [OR] = 3.35, 95% confidence interval [CI] = 1.55–7.24 and OR = 4.14, 95% CI = 1.23–13.94, respectively). Conclusions Intact long-type dupA is a real virulence marker for severe outcomes in Okinawa, Japan. The previous information gained from PCR-based methods without taking long-type dupA into account must be interpreted with caution.

Objectives We aimed to determine whether linked color imaging (LCI), a new image-enhanced endoscopy that enhances subtle differences in mucosal colors, can distinguish the border of endoscopic mucosal atrophy. Methods This study included 30 patients with atrophic gastritis. In endoscopy, we continuously took images in the same composition with both LCI and white light imaging (WLI). In each image, the color values of atrophic and nonatrophic mucosae were quantified using the International Commission on Illumination 1976 (L∗, a∗, b∗) color space. Color differences at the atrophic border, defined as Euclidean distances of color values between the atrophic and nonatrophic mucosae, were compared between WLI and LCI for the overall cohort and separately for patients with Helicobacter pylori infection status. Results We found that the color difference became significantly higher with LCI than with WLI in the overall samples of 90 points in 30 patients. LCI was 14.79 ± 6.68, and WLI was 11.06 ± 5.44 (P < 0.00001). LCI was also more effective in both of the Helicobacter pylori-infected group (P = 0.00003) and the Helicobacter pylori-eradicated group (P = 0.00002). Conclusions LCI allows clear endoscopic visualization of the atrophic border under various conditions of gastritis, regardless of Helicobacter pylori infection status.

Gastric cancer is the second leading cause of cancer-related mortality in the world. Recently, serum Helicobacter pylori antibodies and pepsinogen (PG) have been used for gastric cancer screening. The incidence of gastric cancer in Bhutan is reported to be quite high compared with that in neighbouring countries. In this study, 381 subjects from three areas of Bhutan were assessed for gastric mucosal atrophy and serological parameters. Anti-H. pylori IgG, PG I, PG II and cytotoxin-associated gene A (CagA) antibodies were measured using ELISA. Subjects were classified into four groups according to H. pylori and PG seropositivity: Group A (H. pylorinegative/PG-negative), Group B (H. pylori-positive/PG-negative), Group C (H. pylori-positive/ PG-positive) and Group D (H. pylori-negative/PG-positive). The prevalence of H. pylori in the 381 subjects was 71.1 % (271/381), with high infection rates found in rural areas. The PG I/II ratio was significantly inversely correlated with the atrophy score in the antrum and the corpus (P,0.001). Multivariate analysis showed that the PG status was significantly associated with the presence of atrophy in the corpus. The prevalence of the PG-positive status was significantly higher among H. pylori-positive subjects than among H. pylori-negative subjects (P,0.001). Based on the ABC method, Group B was the most dominant, followed by Group A, Group C and Group D. The high incidence of gastric cancer in Bhutan can be attributed to the high prevalence of H. pylori infection and gastric mucosal atrophy.