Clinical Significance of IgG Antibody Titer against Helicobacter pylori

Background: We clarified the clinical significance of measurement of IgG antibody titers against Helicobacter pylori using data from a nested case–control study from a large-scale cohort study in Japan.
Method: Participants included 36,745 subjects from the Japan Health Center-based Prospective Study who responded to the baseline questionnaire and provided a blood sample. Subjects were aged 40–69 years and were followed over 15 years after initial sampling. Controls were matched to 511 gastric cancer patients. Plasma surface antigen (Hp)-IgG titer was measured using ELISA, and mucosal atrophy was determined by measuring pepsinogen I and II levels.
Results: Seropositive subjects with low Hp-IgG titer and mucosal atrophy showed a higher risk for gastric cancer than high-titer subjects. Odds ratio (OR) referred to cases with true negative IgG titers and no mucosal atrophy. In moderately atrophic subjects, the low titer OR was 19.0, with a 95% confidence interval (CI) of 7.7–46.9, and 12.5 for high titer, with a 95% CI of 5.2–30.0. In severely atrophic subjects, the low titer OR was almost double that of high-titer subjects (OR = 30.2, 95% CI = 12.4–73.7 and OR = 15.9, 95% CI = 6.3–40.3, respectively). These associations were observed more frequently for differentiated than undifferentiated gastric cancer.
Conclusion: Combination assay with Hp-IgG titer and pepsinogens may help identify groups at high risk for gastric cancer. Subjects with low Hp-IgG titer and mucosal atrophy were at extremely high risk for gastric cancer, particularly differentiated cancer. Subjects with this background may require ongoing observation and periodic endoscopic examination for early cancer detection.     

Fasting gastric pH of Japanese subjects stratified by IgG concentration against Helicobacter pylori and pepsinogen status

Background: The clinical significance of Helicobacter pylori antibody titer has been controversial, and the association between the extent of gastric atrophy or acid secretion and H. pylori antibody concentration has not been elucidated. Materials and Methods: Serum pepsinogen, H. pylori antibody concentration, and fasting gastric pH (as an indicator of acid secretion) were measured in 231 patients undergoing upper gastrointestinal endoscopy. “Atrophic” pepsinogen was defined as pepsinogen‐I < 70 ng/mL and pepsinogen‐I/II ratio <3. Other levels of pepsinogen were defined as “normal”. Fasting gastric pH was analyzed in subjects stratified by pepsinogen level and by H. pylori antibody concentration. Results: Helicobacter pylori antibody concentration showed no significant relationship with fasting gastric pH when all subjects were analyzed together. In H. pylori‐seronegative subjects, fasting gastric pH was within the normal range, irrespective of the extent of mucosal atrophy. In H. pylori‐seropositive subjects, H. pylori antibody concentration was positively correlated with fasting gastric pH in subjects with “normal” pepsinogen, but inversely correlated in those with “atrophic” pepsinogen. Particularly in subjects with low H. pylori antibody concentration and atrophic mucosa, a group reportedly at high risk of noncardia cancer, the most impaired acid secretion was shown among subjects with atrophic mucosa. Conclusions: The relationship between acid secretion and H. pylori antibody concentration differs depending on the presence of mucosal atrophy. Our findings provide a possible rationalization for measuring both serum pepsinogen levels and H. pylori antibody concentration in gastric cancer screening.     

Serum Levels of Leptin As Marker For Patients At High Risk of Gastric Cancer

Background:  Serological screening for gastric cancer (GC) may reduce mortality. However, optimal serum markers for advanced gastric precursor lesions are lacking.
Aim:  To evaluate in a case–control study whether serum leptin levels correlate with intestinal metaplasia (IM) and can serve as a tool to identify patients at high risk for GC.
Materials and Methods:  Cases were patients with a previous diagnosis of IM or dysplasia, controls were patients without such a diagnosis. All patients underwent endoscopy. Fasting serum was collected for the measurement of leptin, pepsinogens I/II, gastrin, and Helicobacter pylori . Receiver operating characteristic (ROC) curves and their area under the curve (AUC) were provided to compare serum leptin levels with other serological markers.
Results:  One hundred nineteen cases and 98 controls were included. In cases, the median leptin levels were 116.6 pg/mL versus 81.9 pg/mL in controls ( p  = .01). After adjustment for age, sex and BMI, leptin levels remained higher in cases than in controls ( p  < .005). In multivariate analysis, male sex ( p  = .002), age (<0.001), low pepsinogen levels ( p  = .004) and high leptin levels ( p  = .04) were independent markers for the presence of IM. In addition, a ROC curve including age, sex and pepsinogen I levels had an AUC of 0.79 (95% CI (0.73–0.85)). Adding serum leptin levels increased the AUC to 0.81 (95% CI (0.75–0.86)).
Conclusions:  High leptin levels are associated with an increased risk of IM. Moreover, serum leptin levels are a significant independent marker for the presence of IM. However, in combination with the serological test for pepsinogen I the additional value of serum leptin levels is rather limited.     

LTA 252GG and GA Genotypes are Associated with Diffuse-Type Noncardia Gastric Cancer Risk in the Japanese Population

Background:  There are limited numbers of reports on the association of lymphotoxin-alpha ( LTA ) genotypes with gastric cancer.
Methods:  A nested case–control study was carried out in the longitudinal cohort of atomic bomb survivors using stored sera before diagnosis (mean, 2.3 years) and blood cells. Enrolled were 287 cases with noncardia gastric cancer of diffuse and intestinal types and three controls per case selected from cohort members matched on age, gender, city, and time and type of serum storage and counter-matched on radiation dose.
Results:  LTA 252GG and GA genotypes were associated with the prevalence of Helicobacter pylori IgG seropositivity and higher antibody titer against H. pylori cytotoxin-associated gene A (CagA) protein in controls and they were an independent risk factor for noncardia gastric cancer of diffuse type (RR = 2.8 (95% CI: 1.3–6.3), p  =   .01, and RR = 2.7 (95% CI: 1.5–4.8), p  <   .001), but not for intestinal type, after adjusting for H. pylori IgG seropositivity, CagA antibody titers, chronic atrophic gastritis, smoking, and radiation dose. Cessation of smoking (RR = 0.4 (95% CI: 0.2–0.7), p  <   .001) and never smoking (RR = 0.4 (95% CI: 0.3–0.6), p  <   .001) were both protective for future noncardia gastric cancer. Radiation dose was associated with noncardia gastric cancer in subjects with both the LTA 252G -allele and never smoking/quit smoking histories (RR = 3.8 (95% CI: 1.7–5.9), p  =   .009).
Conclusion:  The LTA 252 genotype is associated with noncardia gastric cancer of diffuse type in Japan and interacted with radiation dose.     

Helicobacter pylori Infection and Gastric Autoimmune Diseases: Is There a Link?

Background. Helicobacter pylori is thought to be involved in atrophic body gastritis. We explored the prevalence of H. pylori infection in asymptomatic subjects with gastric parietal cell antibodies, as well as in patients with pernicious anemia, to evaluate a possible role of H. pylori gastric infection in gastric autoimmunity. Patients and Methods. We studied 79 consecutive asymptomatic subjects with parietal cell antibodies, 24 patients with pernicious anemia, and 66 parietal cell antibody‐negative controls. All patients underwent gastric biopsies for histology and detection of H. pylori. Red blood cell count and volume, serum levels of gastrin, pepsinogen I, iron, folic acid, vitamin B₁₂, and circulating antibodies to H. pylori and to intrinsic factor were also determined. Results. We found an atrophic body gastritis in 14 of the 79 asymptomatic subjects with parietal cell antibodies (18%) and in 2 of the 66 controls (3%) (p = .01). Mean levels of gastrin were increased (p < .0001), while those of pepsinogen were reduced (p < .001) compared with controls. H. pylori was identified at the gastric level and/or circulating anti‐H. pylori antibodies were detected in 46 parietal cell antibody‐positive subjects (58%) compared with 26 controls (39%) (p = .03). In patients with pernicious anemia we found an atrophic body gastritis in 18 of 24 cases (75%) (p < .001 vs. controls). Mean levels of gastrin were markedly increased (p < .0001) and those of pepsinogen I decreased (p < .0001) relative to controls. Only five of these patients (21%) had evidence of H. pylori infection compared with 46 of the parietal cell antibody‐positive subjects (58%) (p = .003) and 26 of the controls (39%). Considering all patients with gastric autoimmunity (i.e. with parietal cell antibodies and/or with pernicious anemia), H. pylori was found in 44 of 72 of those without atrophy (61%) but in 6 of 31 with gastric body atrophy (19%) (p < .001), indicating that H. pylori infection is greatly reduced when gastric acid secretion decreases. Conclusions. The frequent detection of H. pylori infection in subjects with early gastric autoimmunity, indicated by the presence of parietal cell antibodies, suggests that H. pylori could have a crucial role in the induction and/or the maintenance of autoimmunity at the gastric level.     

Toll-Like Receptor 4 +3725 G/C Polymorphism, Helicobacter pylori Seropositivity, and the Risk of Gastric Atrophy and Gastric Cancer in Japanese

Background:  Toll-like receptor 4 (TLR4) Asp299Gly and Thr399Ile polymorphisms were reported to be a risk factor of gastric carcinoma or its precursors in Caucasian and Indian population, but these polymorphisms are absent in Japanese. We investigated the associations of TLR4 +3725 G/C polymorphism, another functional polymorphism of TLR4 , with risk of gastric cancer and gastric atrophy in Japanese.
Materials and Methods:  Study subjects were 583 histologically diagnosed gastric cancer patients and age- and sex-matched 1592 control outpatients, who visited Aichi Cancer Center Hospital from 2001 to 2005. Serum anti- H. pylori IgG antibody and pepsinogens were measured to evaluate H. pylori infection and gastric atrophy, respectively. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by a logistic model.
Results:  Among the seropositive subjects, the age- and sex-adjusted OR of gastric atrophy was 1.17 (95%CI: 0.91–1.50) for G/C , 1.20 (95%CI: 0.76–1.89) for C/C , and 1.18 (95%CI: 0.93–1.49) for G/C + C/C relative to G/G genotype. The age- and sex-adjusted OR of severe gastric atrophy among H. pylori seropositive subjects was 1.43 (95%CI: 0.99–2.06) for G/C , 1.47 (95%CI: 0.76–2.88) for C/C , and 1.43 (95%CI: 1.01–2.04) for G/C + C/C . The OR of gastric cancer compared with gastric atrophy controls was not statistically significant.
Conclusion:  Our study found that TLR4 +3725 G/C polymorphism was a risk factor of severe gastric atrophy in H. pylori seropositive Japanese. Our results underscored the significance of the variations in host innate immunity due to TLR4 polymorphism as genetic predispositions to gastric precancerous lesions in Eastern Asian populations with the same backgrounds.     

Associated Factors of Atrophic Gastritis Diagnosed by Double-Contrast Upper Gastrointestinal Barium X-Ray Radiography: A Cross-Sectional Study Analyzing 6,901 Healthy Subjects in Japan

Background

Double-contrast upper gastrointestinal barium X-ray radiography (UGI-XR) is one of the most widely conducted gastric cancer screening methods. It has been executed to find gastric cancer, but has not been usually executed to detect premalignant atrophic mucosa of stomach. To understand the meaning of UGI-XR-based atrophic gastritis, we analyzed its association with several causative factors including Helicobacter pylori (HP) infection.

Methods

We evaluated 6,901 healthy adults in Japan. UGI-XR-based atrophic gastritis was diagnosed based on the irregular shape of areae gastricae and its expansion in the stomach.

Results

Of the 6,433 subjects with no history of HP eradication and free from gastric acid suppressants, 1,936 were diagnosed as UGI-XR-based atrophic gastritis (mild: 234, moderate: 822, severe: 880). These were univariately associated with serum HP IgG and serum pepsinogen I/II ratio with statistical significance. The multiple logistic analysis calculating standardized coefficients (β) and odds ratio (OR) demonstrated that serum HP IgG (β = 1.499, OR = 4.48), current smoking (β = 0.526, OR = 1.69), age (β = 0.401, OR = 1.49), low serum pepsinogen I/II ratio (β = 0.339, OR = 1.40), and male gender (β = 0.306, OR = 1.36) showed significant positive association with UGI-XR-based atrophic gastritis whereas drinking and body mass index did not. Among the age/sex/smoking/drinking-matched 227 pairs derived from chronically HP-infected and successfully HP-eradicated subjects, UGI-XR-based atrophic gastritis was detected in 99.1% of the former but in only 59.5% of the latter subjects (p<0.0001). Contrastively, UGI-XR-based atrophic gastritis was detected in 13 of 14 HP-positive proton pump inhibitor users (92.9%) and 33 of 34 HP-positive histamine H₂-receptor antagonist users (97.1%), which are not significantly different from gastric acid suppressant-free subjects.

Conclusions

The presence of UGI-XR-based atrophic gastritis is positively associated with Helicobacter pylori infection, current smoking, age, decreased serum pepsinogen I/II ratio, and male gender. Eradication of Helicobacter pylori seems to superficially improve UGI-XR-based atrophic gastritis whereas intake of gastric acid suppressants does not.     

When Does Gastric Atrophy Develop in Japanese Children?

Background: Long-term Helicobacter pylori infection causes inflammatory sequelae such as atrophy and intestinal metaplasia in the stomach, which is thought to increase the risk of developing gastric malignancy. We previously reported that gastric atrophy can develop in Japanese children with H. pylori infection, predominantly in the antrum. However, detailed data about the age of children with atrophy are largely lacking.
Methods and results: In the present study, 131 children (79 boys) with H. pylori infection were re-analyzed for an association between age and the grade of gastric atrophy. The gastric antrum was histologically evaluated in all 131 patients and the corpus in 46 patients. Grade 2 and 3 antral atrophy was observed in 13 and one patients, respectively: the mean age was 12.1 years. Two patients (11 and 14 years old) had grade 2 corpus atrophy but no patients had grade 3. No significant difference was found in age among patients with grade 0, 1 and 2 or 3 atrophy in the antrum ( p =  .97) and in the corpus ( p =  .59). None of the patients with grade 2 or 3 atrophy had intestinal metaplasia either in the antrum or in the corpus.
Conclusions: The results of the present study require a careful interpretation because of the retrospective analysis. In high-risk countries of gastric cancer, however, eradicating H. pylori in childhood could prove more effective in preventing gastric atrophy, ultimately, the development of cancer.     

Interleukin-2 gene polymorphisms associated with increased risk of gastric atrophy from Helicobacter pylori infection

BACKGROUND: Gastric atrophy induced by Helicobacter pylori is thought to predispose patients to noncardiac gastric cancer development. However, the host genetic factors that influence the progression of gastric atrophy have not been elucidated. In this study, we examined the effects of cytokine polymorphisms on H. pylori-induced gastric atrophy. METHODS: Blood samples were taken from 454 Japanese subjects. The interleukin-2 (IL-2; T-330G), IL-4 (C-33T), and IL-13 (C-1111T) polymorphisms were genotyped by polymerase chain reaction with confronting two-pair primers (PCR-CTPP). Anti-H. pylori IgG antibody and pepsinogen I and II were measured to diagnose H. pylori infection and atrophic gastritis. RESULTS: The odds ratios (ORs) for the association between IL-2 polymorphism [OR = 2.78, 95% CI (confidence interval) = 1.26-6.17 (T/T to G/G)] or IL-4 polymorphism [OR = 2.22, 95% CI = 1.01-4.89 (T/C to C/C)] were increased significantly with gastric atrophy, whereas the corresponding OR of IL-13 polymorphism was decreased with gastric atrophy [OR = 0.61, 95% CI = 0.39-0.96 (C/T and T/T to C/C)]. There were no significant H. pylori seropositivity-related differences between these polymorphisms. We examined the relationship between these polymorphisms and gastric atrophy separately in H. pylori-seropositive and -seronegative groups. In the H. pylori-seropositive group, the IL-2 T/T (OR = 2.78, 95% CI = 1.12-6.93) had a significant association with gastric atrophy. CONCLUSIONS: These results reveal that the IL-2 gene polymorphism is associated with an increased risk of gastric atrophy induced by H. pylori infection and might predispose to gastric cancer.     

No Association of Coffee Consumption with Gastric Ulcer,Duodenal Ulcer,Reflux Esophagitis,and Non-Erosive Reflux Disease: A Cross-Sectional Study of 8,013 Healthy Subjects in Japan

Probably due to caffeine-induced gastric acid secretion, negative effects of coffee upon various upper-gastrointestinal diseases have been precariously accepted, despite the inadequate epidemiological evidence. Our aim is to evaluate the effect of coffee consumption on four major acid-related diseases: gastric ulcer (GU), duodenal ulcer (DU), reflux esophagitis (RE), and non-erosive reflux disease (NERD) based on the large-scale multivariate analysis. Of the 9,517 healthy adults, GU, DU, and RE were diagnosed by endoscopy, and NERD was diagnosed by the symptoms of heartburn and regurgitation without esophageal erosion. Associations between coffee consumption and the four disorders were evaluated, together with age, gender, body mass index (BMI), Helicobacter pylori (HP) infection status, pepsinogen I/II ratio, smoking, and alcohol. We further performed meta-analysis using the random effects model to redefine the relationship between coffee intake and peptic ulcer disease. The eligible 8,013 study subjects comprised of 5,451 coffee drinkers and 2,562 non-coffee drinkers. By univariate analysis, age, BMI, pepsinogen I/II ratio, smoking, and alcohol showed significant associations with coffee consumption. By multiple logistic regression analysis, positively correlated factors with significance were HP infection, current smoking, BMI, and pepsinogen I/II ratio for GU; HP infection, pepsinogen I/II ratio, and current smoking for DU; HP non-infection, male, BMI, pepsinogen I/II ratio, smoking, age, and alcohol for RE; younger age, smoking, and female for NERD. The meta-analyses could detect any association of coffee consumption with neither GU nor DU. In conclusion, there are no significant relationship between coffee consumption and the four major acid-related upper gastrointestinal disorders.     

Prevalence and risk factors of atrophic gastritis and intestinal metaplasia in a Korean population without significant gastroduodenal disease

Background and Aim: The prevalence of gastric cancer and Helicobacter pylori infection is unacceptably high in Korea. This study was performed to evaluate the prevalence of atrophic gastritis (AG) and intestinal metaplasia (IM) and to identify their risk factors with respect to H. pylori virulence factors, and environmental and host factors, in Korean population without significant gastroduodenal disease.
Methods: The study cohort consisted of 389 subjects (≥ 16 years). AG and IM were scored histologically using the Sydney classification in the antrum and body, respectively. Prevalences and bacterial factors (i.e. cagA , vacA m1, and oipA ), environmental factors (i.e. smoking and alcohol), and host factors (i.e. genetic polymorphisms of IL-1B- 511, IL-1RN , TNF-A -308, IL-10 -592, IL-10 -819, IL-10 -1082, IL-8 -251, IL-6 -572, GSTP1 , p53 codon 72, and ALDH2 ) were evaluated.
Results: Prevalences of AG in the antrum and body were 42.5% and 20.1%, and those of IM were 28.6% and 21.2%, respectively. The presences of AG and IM were significantly higher in H. pylori -positive than in the H. pylori -negative subjects. Multivariate analysis showed that the risk factors for AG were H. pylori infection, age ≥ 61 years, and cagA and vacA m1 positivity. For IM the risk factors were H. pylori infection, age ≥ 61 years, a smoking history (rather than current smoking), strong spicy food, occupation (unemployed or nonprofessional vs. professional), and the presence of IL10- 592 C/A as opposed to A/A. In addition, IL6- 572 G carrier was found to have a protective effect against IM development as compared with C/C.
Conclusion: H. pylori infection was most important risk factor of AG and IM. Bacterial factors were found to be important risk factor for AG but environmental and host factors were more important for IM.     

Prevalence and clinicopathologic characteristics of gastric cardia cancer in South Korea

Background and Aim: Western reports have suggested that the prevalence of gastric cardia cancer (GCC) has been increasing, and indicated some differences between GCC and gastric noncardia cancer (GNCC). However, few studies have been conducted in Asia. The aims of this study were to estimate the prevalence of GCC and to evaluate differences of clinicopathologic characteristics between GCC and GNCC in South Korea. Methods: This study was single‐center case–control study. A total of 829 patients with gastric cancer and 270 controls were enrolled between 2003 and 2011. Baseline characteristics, Helicobacter pylori (H. pylori) infection status, and histologic characteristics were compared among three groups (GCC, GNCC, and control). Results: Sixty cases (7.2%) of gastric cancer were located in cardia. Multivariate analysis showed that male odds ratio (OR, 5.72; 95% CI, 1.72–19.07; p = .005) and cigarette smoking (OR, 5.38; 95% CI, 1.39–20.90; p = .015) were risk factors of GCC in comparison with control group, but H. pylori infection rate was not significant. In the case of GNCC, cigarette smoking (OR, 3.87; 95% CI, 1.81–8.29; p < .001), past alcohol intake (OR, 2.82; 95% CI, 1.28–6.20; p = .010), intestinal metaplasia (OR, 3.22; 95% CI, 2.00–5.17; p < .001), and H. pylori infection (OR, 3.06; 95% CI, 1.90–4.93; p < .001) were risk factors of GNCC. Gastroesophageal reflux disease symptoms were higher in the GNCC (21.2%) than control group (13.5%) (p = .008). However, in the case of GCC, they were similar between the GCC (12.7%) and control group (p = .872). According to multivariate analysis, history of H. pylori eradication (OR, 0.34; 95% CI, 0.19–0.61; p < .001) was associated with a protective effect on GNCC. GCC showed higher depth of invasion (p = .038) and frequent distant metastasis (p = .012) than GNCC. Conclusion: In this referral center based study, the prevalence of GCC was 7.2% in South Korea. Risk factors and clinicopathologic characteristics for GCC and GNCC were different, supporting that the pathophysiology is different in the development of GCC and GNCC.     

Serum pepsinogen level,atrophic gastritis and the risk of incident pancreatic cancer—A prospective cohort study

Background: Pancreatic cancer is a highly fatal disease without screening tests. Studies have suggested possible etiologic similarities between gastric and pancreatic cancers. Atrophic gastritis, a pre-malignant condition for gastric cancer, is characterized by low serum pepsinogen I (SPGI) level. We hypothesized that low SPGI level may be associated with an increased risk of pancreatic cancer and be a useful biomarker for the disease. Methods: Our analytic cohort included 20,962 participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) who had SPGI level measured. Of these, 1663 (7.9%) subjects had low SPGI levels (<25 μg/l) and were invited for gastroscopy which was completed in 1059 (63.7%) participants. Atrophic gastritis was histologically confirmed in 1006 (95.0%) subjects. We used Cox proportional hazards regression to calculate the hazard ratios (HR) and 95% confidence intervals (CI) for pancreatic cancer. Results: During follow-up of up to 16.3 years (mean = 10.8 years; 226,325 person-years), 227 incident pancreatic cancers were diagnosed. The incidence rates were 9.9, 11.3, and 12.7 per 10,000 person-years of follow-up for participants with normal pepsinogen level (≥25 μg/l), low pepsinogen level and histologically confirmed atrophic gastritis, respectively. Compared to subjects with normal pepsinogen levels, there was no statistically significant increased risk of pancreatic cancer among subjects with low pepsinogen level (adjusted HR = 1.01; 95% CI: 0.63–1.62) or those with histologically confirmed atrophic gastritis (adjusted HR = 1.13; 95% CI: 0.66–1.95). Conclusions: Atrophic gastritis, serological or histological, is not associated with increased risk of pancreatic cancer. These findings do not provide any evidence for potential usefulness of SPGI for pancreatic cancer screening.     

Comparison of a Stool Antigen Test and Serology for the Diagnosis of Helicobacter pylori Infection in Mass Survey

Background: Serum antibody to Helicobacter pylori is tested in mass screening for gastric cancer along with the level of serum pepsinogens (PG) I and II. Recently, stool antigen tests have been developed as a new non-invasive test. We examined H. pylori infection by both serology and stool antigen test in a mass survey and compared the results to estimate applicability of stool antigen test for mass survey.
Methods: A total of 994 healthy adults who received mass survey in April 2005 were tested. There were 379 men and 615 women, and the mean age was 57.7 years old. Stool samples were used to measure a H. pylori- specific antigen by enzyme immunoassay. Serum samples were tested for the prevalence of IgG antibody to H. pylori , and the level of PGs I and II was also measured to determine the presence of atrophic gastritis.
Results: Infection of H. pylori was defined as positive 61.4% and 56.4% by serology and stool antigen test, respectively. The concordance of both tests was not affected by gender and age of the subjects but difference was seen in subjects with atrophic gastritis. In particular, positivity of stool antigen test (81.8%) was significantly lower than that of serology (88.7%, p  < .05) in 303 subjects with severe atrophic gastritis.
Conclusions: Stool antigen test, which detects present but not previous infection of H. pylori , would be applicable to diagnose H. pylori infection in mass survey. Usefulness of stool antigen tests for the screening of gastric cancer should be examined.     

Atrophic Changes of Gastric Mucosa Are Caused by Helicobacter pylori Infection Rather Than Aging: Studies in Asymptomatic Japanese Adults

Background. The current study was designed to evaluate the effect of aging and Helicobacter pylori infection on the gastric mucosa in asymptomatic Japanese adults.
Materials and Methods. Eighty-five asymptomatic healthy adults were recruited from a health-screening center in Sapporo. All subjects underwent endoscopy and gastric biopsy, and serum was obtained for IgG antibodies to H. pylori , serum gastrin, and pepsinogen levels.
Results. The prevalence of atrophic change of the gastric mucosa assessed by pathological findings increased with age (49% in the 30- to 39-year-old group compared to 89% in those 60 years and older, p < .001). The frequency of intestinal metaplasia also increased with age (38% in the 30- to 39-year-old group compared to 82% in those 60 years and older, p < .001). In contrast, the frequency of atrophic gastritis and intestinal metaplasia was extremely low in the H. pylori seronegative group regardless of age. Mean serum gastrin level in H. pylori -positive adults was significantly greater than in those who were H. pylori -negative (114.3 ± 11.2 compared to 65.8 ± 6.5 pg/ml, p < .03). The serum pepsinogen I-II ratio was significantly lower in those with H. pylori infection than in those without (3.1 compared to 6.6, p < .0001).
Conclusions. These results suggest that the chronological changes in the gastric mucosa in Japanese individuals are either entirely related to H. pylori infection or the process is greatly accelerated by H. pylori infection.     

Effect of body-mass index on the risk of gastric cancer: A population-based cohort study in A Japanese population

BackgroundBody fatness and weight gain are considered probable causes of gastric cancer, specifically in the cardia region. However, limited evidence is available in Asia, where the burden of gastric cancer is high. The objective of this study was to determine an association between body-mass index (BMI) and gastric cancer risk using a large population prospective cohort.Methods92,056 subjects enrolled in the Japan Public Health Center-based prospective Study who reported their height and weight were followed up until the end of 2013. A Cox proportional hazards model was used to estimate the risk for gastric cancer and its subsite based on baseline BMI. A subgroup analysis was conducted taking account of Helicobacter pylori (H. pylori) infection and atrophic gastritis status.Results2,860 gastric cancer cases (2,047 men, 813 women), 307 proximal gastric cancer cases (244 men, 63 women), and 1967 distal gastric cancer cases (1,405 men, 562 women) were found during the follow-up period. Among men, baseline BMI ≥ 27 kg/m² increased the risk of overall gastric cancer (hazards ratio (HR) 1.23, 95% confidence interval (CI) 1.00–1.53). For both sexes, U-shaped increase in the risk was observed for proximal gastric cancer. Subgroup analysis showed a statistically significant association between the risk of proximal gastric cancer and BMI ≥ 27 kg/m² among those who were atrophic gastritis positive, H. pylori antibody positive, and those who tested positive to either or both atrophic gastritis and H. pylori antibody.ConclusionOur result suggests that gastric cancer risk increases for men with BMI ≥ 27 kg/m².     

Helicobacter pylori genotyping and sequencing using paraffin-embedded biopsies from residents of colombian areas with contrasting gastric cancer risks

Background:   cagA -positive and vacA s1 and m1 genotypes of Helicobacter pylori are associated with an elevated risk of gastric cancer (GC). We determined these genotypes using paraffin-embedded gastric biopsy specimens harvested from infected individuals and compared genotype distributions in two Colombian populations residing in geographic regions with a high and low incidence of GC.
Methods:   DNA from paraffin-embedded gastric biopsies from 107 adults was amplified using primers specific for cagA , for the cag 'empty site', for the s and m alleles of vacA , and for H. pylori 16S rRNA.
Results:   H. pylori infection was detected by molecular assays in 97 (90.7%) biopsies. Complete genotyping of cagA and vacA was achieved in 94 (96.9%) cases. The presence of cagA was detected in 78 of 97 cases (80.4%); when considered separately, cagA and vacA s regions were not significantly associated with a particular geographic area. The vacA m1 allele and s1m1 genotypes were more common in the area of high risk for GC ( p =  .037 and p  = .044, respectively), while the vacA m2 allele and s2m2 genotypes were more prevalent in the low-risk area. The prevalence of the combination of cagA -positive, vacA s1m1 genotypes was 84.3% and 60.5% for high and low risk areas, respectively ( p =  .011).
Conclusions:  H. pylori cagA and vacA genotyping from paraffin-embedded gastric biopsies permitted reliable typability and discrimination. The more virulent cagA- positive s1m1 strains, as well as vacA m1 genotype, were more prevalent in high risk than in low risk areas, which may contribute to the difference in GC risk between those two regions.     

Association of Helicobacter pylori-related distal gastric cancer with the HLA class II gene DQB10602 and cagA strains in a southern European population

BACKGROUND: Distinct human leukocyte antigen (HLA)-DQ genes have been associated with an increased or reduced risk for gastric cancer, but its association with Helicobacter pylori status is controversial. In the present study we evaluated the influence of host HLA DQA1 and DQB1 loci, H. pylori genotype, and socio-economic factors on predicting H. pylori-associated distal gastric cancer in a southern European population. MATERIAL AND METHODS: In a prospective case-control (1 : 2) study, 42 patients with H. pylori-associated distal gastric cancer were matched by age (+/-5 years) and gender to 84 patients with H. pylori-associated benign gastroduodenal disease (controls). The level of education received, smoking status, alcohol consumption, origin and familial history of gastric cancer were registered at inclusion. HLA DQA1 and DQB1 typing and H. pylori genotyping were determined from endoscopic gastric mucosal biopsies. RESULTS: Compared with control patients, a positive association with cagA(+) strains (p < .002) and a negative association with vacA-s2 strains (p < .02) was found in patients with distal gastric cancer. At the DQB1 locus, the (*)0602 allele was more frequent in distal gastric cancer than in controls (26.2% vs. 4.8%; p < .005). After correction for multiple comparisons (exact multiple regression analysis) the cagA(+) status and the DQB1(*)0602 allele were associated with an increased distal gastric cancer risk (OR 3.7; 95% CI = 1.33-12.26 and OR 4.82; 95% CI = 1.24-19.83, respectively) whereas the vacA-s2 status was associated with a decreased risk (OR 0.33; 95% CI = 0.10-0.94). CONCLUSION: Our findings suggest that in the H. pylori-infected southern European population, the cagA genotype and the HLA-DQB1(*)0602 gene confer an increased risk for distal gastric cancer.     

Helicobacter pylori CagA Status,Mucosal Oxidative Damage and Gastritis Phenotype: A Potential Pathway to Cancer?

Background. Oxidative DNA damage is associated with Helicobacter pylori infection, atrophy and intestinal metaplasia. H. pylori‐cagA‐positive strains are associated with the highest risk of gastric cancer. Aims. To ascertain whether cagA‐positive H. pylori infection correlates with higher concentrations of 8OHdG and the presence of precancerous changes. Patients and Methods. 118 patients were studied (65M/53F, age 61 ± 14 years). Twelve were H. pylori‐negative. Among the H. pylori‐positive patients, 34 were cagA‐positive and 40 were cagA negative. In 32 patients H. pylori had been eradicated at least 6 months before endoscopic sampling. The phenotype of the gastritis (atrophic compared with nonatrophic, with and without intestinal metaplasia) was scored in biopsy samples obtained from the antrum, corpus, and angularis incisura. In antral biopsy samples, 8‐hydroxydeoxyguanosine was assessed by HPLC (electrochemical detector). CagA status was determined by PCR. Results. The highest scores for both mononuclear inflammation and activity of gastritis were significantly associated with cagA status (p = 0.036 antrum and p = 0.02 corpus). cagA‐positive infection significantly correlated with a higher prevalence of atrophic‐metaplastic lesions (p = 0.04). cagA‐positive patients had higher 8‐hydroxydeoxyguanosine levels than both cagA‐negative and H. pylori‐negative cases (p = 0.01). The 8‐hydroxydeoxyguanosine levels were significantly higher in multifocal atrophic gastritis (p = 0.04). The odds ratio for cagA‐positive patients having 8OHdG levels above a cut‐off calculated on the basis of the ROC curves were 7.12, overall, reaching 11.25 when only patients younger than 50 were considered. Conclusions. cagA‐positive patients were characterized: first, for higher scores for gastritis, activity and atrophic and metaplastic lesions; and second for greater oxidative DNA damage overall, at younger age and in the presence of multifocal atrophy. This setting may represent a cancer‐prone biological context.