Pylori Antibody Titers Research Articles

Trends in the prevalence of atrophic gastritis and Helicobacter pylori infection over a 10‑year period in Japan: The ROAD study 2005‑2015.

Few large population-based studies have examined the prevalence of atrophic gastritis (AG) and Helicobacter pylori infection in Japan. The purpose of the present study was to estimate the prevalence of AG and H. pylori infection by age, in addition to investigating their change rates from 2005 to 2016 in Japan using data from a large population-based cohort. A total of 3,596 participants [1,690 in the baseline survey (2005-2006) and 1,906 at the fourth survey (2015-2016)] aged 18 to 97 years were included in the cohort. The prevalence of AG and H. pylori infection were examined at baseline and in the fourth survey based on serological tests for the H. pylori antibody titer and pepsinogen levels. The prevalence of AG and H. pylori infection were 40.1% (men, 44.1%; women, 38.0%) and 52.2% (men, 54.8%; women, 50.8%), respectively, at baseline. AG seropositivity rates showed a significant decrease from 40.1 to 25.8% in 10 years. H. pylori seropositivity rates decreased significantly from 52.2 to 35.5% in 10 years. Stratified for age, the prevalence of AG showed an increasing trend with age, whereas the prevalence of H. pylori infection increased with aging, except for in the elderly group, showing an inverted U-shaped association. In this population-based, cross-sectional study with a 10-year interval survey, the prevalence of AG and H. pylori infection decreased significantly. This change may influence the prevalence of H. pylori-related diseases, including extra-gastric disorders associated with H. pylori-induced systemic subclinical inflammation and hypochlorhydria, such as colorectal neoplasia and arteriosclerosis.

Risk of gastric cancer development according to the combination of anti–Helicobacter pylori antibody titer and degree of atrophic gastritis.

297 Background: Helicobacter pylori is known as the main risk factor for gastric cancer. It is also well known that gastric atrophy which is the result of long-term H. pylori infection induces spontaneous regression of H. pylori infection and such atrophic status with negative H. pylori infection is related with high risk of gastric cancer, as in so called “ABC method”. However the implication of anti- H. pylori antibody titer is not well investigated. This study was designed to identify the risk for gastric cancer according to the combination of level of anti- H. pylori antibody titer and gastric atrophy. Methods: Those who had health checkups including upper endoscopy and serum anti- H. pylori antibody test between 2003 and 2018 were enrolled. Among them, those who had positive results for anti- H. pylori antibody were included in this study and those who had followed up for less than 1 year were excluded. Kimura-Takemoto classification C3 or more was defined as gastric atrophy. Individuals were classified into 4 groups: low B (low titer without atrophy), high B (high titer without atrophy), high C (high titer with atrophy), and low C (low titer with atrophy). Their risks for gastric cancer were compared under adjustment with other risk factors. Results: During median 5.7 years of follow-up, among 28,311 subjects, 231 developed new gastric cancer. Among them, 159 were intestinal type, 68 were diffuse type, and 4 were type-unknown. For intestinal type gastric cancer, high C group and low C group showed significantly high risk compared with low B group (high C: aHR 10.516; 95% CI, 6.485-17.054) (low C: aHR 11.191; 95% CI, 7.096-17.649). However, for diffuse type gastric cancer, high B group showed higher risk compared with low B group (aHR, 1.713; 95% CI, 1.021-2.875). When those two factors were taken separately, grade of atrophy was related with the risk for intestinal type gastric cancer (aHR, 2.047; 95% CI, 1.862-2.251), while the level of anti- H. pylori antibody titer was related with the risk for diffuse type gastric cancer (aHR, 1.158; 95% CI, 1.041-1.288). Conclusions: Among those with current H. pylori infection, high anti- H. pylori antibody titer is related with diffuse type gastric cancer. The risk was prominent especially among those without atrophy. Therefore, those with high level of anti- H. pylori antibody titer need to be considered as high risk group even without atrophy and should be considered as good candidates for H. pylori eradication and intensive screening.

Long-term Response of Helicobacter pylori Antibody Titer After Eradication Treatment in Middle-aged Japanese: JPHC-NEXT Study.

Helicobacter pylori (H. pylori) is an established causative factor of gastric cancer. Although the expansion of insurance coverage has led to an increase in the number of patients treated for H. pylori, the population impact of eradication treatment for H. pylori has been scarcely investigated. This study aimed to clarify the long-term responses of H. pylori antibody titer after eradication treatment using large scale cross-sectional data from the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT Study). A total of 55,282 Japanese participants aged 40 to 74 years residing in 16 areas provided blood samples from 2011 through 2016. From these, treated (n = 6,276) and untreated subjects who were seropositive for H. pylori or had serological atrophy (n = 22,420) formed the study population (n = 28,696). Seropositivity was defined as an anti-H. pylori IgG titer of ≥10 U/mL. Antibody level was compared among subjects according to self-reported treatment history as untreated, and treated for less than 1 year (<1Y), 1 through 5 years (1-5Y), and 6 or more years ago (6Y+). Median serum antibody titer was 34.0 U/mL, 7.9 U/mL, 4.0 U/mL, and 2.9 U/mL for the untreated, <1Y, 1-5Y, and 6Y+ groups, respectively. While those treated for H. pylori within the previous year had a 76.8% lower antibody titer compared to untreated subjects, approximately 41% of subjects were still seropositive. A significant reduction in H. pylori antibody titer occurs within 1 year after eradication treatment, but that a long period is needed to achieve complete negative conversion.

Association between Active Helicobacter pylori Infection and Glaucoma: A Systematic Review and Meta-Analysis.

Background: Glaucoma is the second most common cause of blindness worldwide affecting almost 70 million individuals. Helicobacter pylori (H. pylori) is a widespread pathogen with systematic pathogenicity. This meta-analysis aimed to estimate the contradictory data regarding a potential association between active H. pylori infection and glaucoma. Materials and Methods: A research in MEDLINE/PubMed and Google Scholar was conducted and original studies investigating the relationship between H. pylori infection and glaucoma were included. Analysis was performed with random effects model. The main outcome was the odds ratio (OR) with 95% confidence intervals (CI) of H. pylori infection as a risk factor for glaucoma. A parallel analysis studied the role of active infection as indicated by histology and the titer of anti-H. pylori antibodies. For the anti-H. pylori antibody titers, weighted mean differences (WMD) were estimated between patients and controls. Results: Fifteen studies were included, with 2664 participants (872 patients with glaucoma and 1792 controls), divided into primary open-angle glaucoma (POAG), normal tension glaucoma (NTG) and pseudo-exfoliation glaucoma (PEG). The association between H. pylori infection and overall glaucoma was significant (OR = 2.08, CI 95% 1.48–2.93) with moderate heterogeneity (I2 = 61.54%). After stratification by glaucoma subtype, heterogeneity was eliminated in the NTG subgroup. Studies with healthy controls, and controls with anemia yielded very low or no heterogeneity, respectively. Gastric biopsy to document active H. pylori infection yielded the highest OR (5.4, CI: 3.17–9.2, p < 0.001) and null heterogeneity. For anti-H. pylori antibody titers, there was a significant difference in WMD between patients and controls (WMD 15.98 IU/mL; 95% CI: 4.09–27.87; p = 0.008); values were greater in glaucoma patients, with high heterogeneity (I2: 93.8%). Meta-regression analysis showed that mean age had a significant impact on glaucoma (p = 0.037). Conclusions: Active H. pylori infection may be associated with glaucoma with null heterogeneity, as, beyond histology, quantified by anti-H. pylori titers and increases with age.

Epstein-Barr virus-associated gastric carcinomas developed after successful eradication of Helicobacter pylori.

Epstein-Barr virus-associated gastric carcinoma (EBVaGC) can develop in gastric mucosa affected by Helicobacter pylori (H. pylori)-induced atrophic gastritis. However, it is unclear whether EBVaGC can develop in gastric mucosa after successful eradication of H. pylori. We report 3 cases of EBVaGC discovered more than 5years after successful eradication of H. pylori. All 3 cases are men with a history of smoking. The periods from successful eradication to development of EBVaGC were 18, 8, and 9years, respectively. Their tumors were mainly depressed lesions located in the gastric corpus. Two patients had intramucosal cancer and the other had advanced gastric cancer. Mucosal atrophy was present in the background gastric mucosa of all of three, and the anti-H. pylori antibody titer in each patient had fallen to < 3U/mL. These cases indicate that EBVaGC can occur after successful eradication of H. pylori.

Gastric Cancer Screening by Combined Determination of Serum Helicobacter pylori Antibody and Pepsinogen Concentrations: ABC Method for Gastric Cancer Screening.

Objective:Gastroscopy combined with gastric mucosa biopsies is currently regarded as a gold standard for diagnosis of gastric cancer. However, its application is restricted in clinical practice due to its invasive property. A new noninvasive population screening process combining the assay of anti-Helicobacter pylori antibody and serum pepsinogen (PG) (ABC method) is adopted to recognize the high-risk patients for further endoscopy examination, avoiding the unnecessary gastroscopy for most population and saving the cost consumption for mass screening annually. Nevertheless, controversies exist for the grouping of ABC method and the intervals of gastroscopy surveillance for each group. In this review, we summarized these popular concerned topics for providing useful references to the healthcare practitioner in clinical practice.Data Sources:The PubMed databases were systematically searched from the inception dates to November 22, 2017, using the keywords “Helicobacter pylori,” “Pepsinogens,” and “Stomach Neoplasms.”Study Selection:Original articles and reviews on the topics were selected.Results:Anti-H. pylori antibody and serum PG concentration showed significant changes under the different status of H. pylori infection and the progression of atrophic gastritis, which can be used for risk stratification of gastric cancer in clinic. In addition, anti-H. pylori antibody titer can be used for further risk stratification of gastric cancer contributing to determine better endoscopy surveillance interval.Conclusions:The early detection and diagnosis of gastric cancer benefit from the risk stratification, but the cutoff values for H. pylori antibody and serum PG concentration require further modification.

Plasma Helicobacter pylori Antibody Titers and Helicobacter pylori Infection Positivity Rates in Patients with Gallbladder Cancer or Cholelithiasis: a Hospital-Based Case-Control Study

ObjectiveGallbladder cancer is the commonest gastrointestinal cancer in northern Indian women. Some studies have examined the association between Helicobacter pylori infection and gallbladder cancer risk, but findings have been inconsistent. We aimed to examine the association between H. pylori infection and gallbladder cancer in Indian people.Materials and MethodsWe conducted a hospital-based case-control study including 100 gallbladder cancer patients with gallstones who were 32 to 79 years old (cases; 72 women and 28 men), and 100 cholelithiasis patients aged 14 to 75 years (controls; 65 women and 35 men). All patients had a diagnosis of gallbladder cancer or cholelithiasis at the Sanjay Gandhi Post Graduate Institute of Medical Sciences in Lucknow having a high gallbladder cancer incidence in northern India, from May 2014 through July 2017. Plasma samples were collected from all patients before surgical treatment. Plasma H. pylori antibody titer was measured by the latex agglutination method and an autoanalyzer. H. pylori infection was defined as antibody titer ≥10 U/mL. Plasma antibody titers and H. pylori infection positivity rates were compared between cases and controls.ResultsMean plasma antibody titers (standard deviation, range) were 11.1 U/mL (11.6, 0–78) in cases and 13.6 U/mL (23.0, 1–164) in controls. H. pylori infection positivity rates were 41% and 42% in cases and controls, respectively. No significant differences in antibody titers or H. pylori infection positivity rates were found between cases and controls.ConclusionsWe found no evidence of H. pylori infection as an important risk factor for gallbladder cancer in Indian people.

Helicobacter pylori infection status had no influence on upper gastrointestinal symptoms: a cross-sectional analysis of 3,005 Japanese subjects without upper gastrointestinal lesions undergoing medical health checkups

BackgroundThis study aimed to evaluate the influence of Helicobacter pylori infection and its eradication on the upper gastrointestinal symptoms of relatively healthy Japanese subjects.MethodsA total of 3,005 subjects (male/female: 1,549/1,456) undergoing medical health checkups were enrolled in the present study, at five hospitals in Saga, Japan, from January to December 2013. They had no significant findings following upper gastrointestinal endoscopy. All subjects completed a questionnaire that addressed a frequency scale for symptoms of gastroesophageal reflux disease. The questionnaire comprised seven questions regarding reflux symptoms and seven regarding acid-related dyspepsia, which were answered with a score based on the frequency of symptoms. Helicobacter pylori infection was identified by a rapid urease test and/or H. pylori antibody titer, and an eradication history was confirmed by the subjects’ medical records.ResultsHelicobacter pylori infection was positive in 894 subjects out of 3,005 (29.8%). Eradication of Helicobacter pylori was successfully achieved in 440 subjects of 458 treated. Helicobacter pylori infection had no influence on the acid-related dyspepsia evaluated by the questionnaire, whereas the mean reflux score was relatively high in the Helicobacter pylori native negative subjects compared to Helicobacter pylori native positive. Eradication of Helicobacter pylori and time span after the eradication had no effect on the upper gastrointestinal symptoms evaluated by the questionnaire.ConclusionHelicobacter pylori infection and history of eradication did not affect acid-related dyspepsia symptoms in Japanese healthy subjects.

Actual Status of Involvement of Helicobacter pylori Infection That Developed Gastric Cancer from Group A of ABC (D) Stratification - Study of Early Gastric Cancer Cases That Underwent Endoscopic Submucosal Dissection

Background/Aims: Patients who are Helicobacter pylori antibody negative and have normal pepsinogen (PG) levels (group A of ABC (D) stratification) are considered unlikely to develop gastric cancer. This study aimed to clarify the involvement (uninfection, present infection or previous infection) of H. pylori in group A patients with early gastric cancer who underwent endoscopic submucosal dissection (ESD) by examining their background gastric mucosa endoscopically and histologically. Methods: This study included 166 patients with gastric cancer who were treated by ESD. Patients were classified according to PG levels and H. pylori antibody titers. Three biopsies (greater curvature of the antrum, lesser curvature of the middle corpus and greater curvature of the middle corpus) from group A were histologically analyzed and compared with those of groups B, C, D and after eradication). Results: In group A (34 patients), 32 patients had endoscopic atrophy (group A′). Histological neutrophil activity, chronic inflammation and atrophy scores were lower in group A′ than in other groups. Group A′ scores were similar to those of the after eradication group. Conclusion: Most of the group A patients with early gastric cancer were not uninfected with H. pylori, but had previous infections, thus carrying carcinogenic risk.

6 Marked Amount of Gray-Zone H. pylori Antibody Titer Cases Have High Risks of Gastric Cancer Due to Those Mucosal Atrophy

6 Marked Amount of Gray-Zone H. pylori Antibody Titer Cases Have High Risks of Gastric Cancer Due to Those Mucosal Atrophy

Declining trends in prevalence of Helicobacter pylori infection by birth-year in a Japanese population.

Gastric cancer incidence and mortality have been decreasing in Japan. These decreases are likely due to a decrease in prevalence of Helicobacter pylori infection. Our aim was to characterize the trends in prevalence of H. pylori infection focused on birth-year. We carried out a cross-sectional study that included 4285 subjects who were born from 1926 to 1989. We defined H. pylori infection by the serum H. pylori antibody titer. Individuals having H. pylori infection and those with negative H. pylori antibody titer and positive pepsinogen test were defined as high-risk individuals for gastric cancer. We estimated the birth-year percent change (BPC) of the prevalence by Joinpoint regression analysis. The prevalence of H. pylori infection among the subjects born from 1927 to 1949 decreased from 54.0% to 42.0% with a BPC of -1.2%. It was followed by a rapid decline in those born between 1949 (42.0%) and 1961 (24.0%) with a BPC of -4.5%, which was followed by those born between 1961 (24.0%) and 1988 (14.0%) with a BPC of -2.1%. The proportion of high-risk individuals for gastric cancer among the subjects born from 1927 to 1942 decreased from 62.0% to 55.0% with a BPC of -0.8%. A subsequent rapid declining trend was observed in those born between 1942 (55.0%) and 1972 (18.0%) with a BPC of -3.6%, and then it became stable. These remarkable declining trends in the prevalence of H. pylori infection by birth-year would be useful to predict the future trend in gastric cancer incidence in Japan.

Helicobacter pylori Antibody Titer and Gastric Cancer Screening.

The “ABC method” is a serum gastric cancer screening method, and the subjects were divided based on H. pylori serology and atrophic gastritis as detected by serum pepsinogen (PG): Group A [H. pylori (−) PG (−)], Group B [H. pylori (+) PG (−)], Group C [H. pylori (+) PG (+)], and Group D [H. pylori (−) PG (+)]. The risk of gastric cancer is highest in Group D, followed by Groups C, B, and A. Groups B, C, and D are advised to undergo endoscopy, and the recommended surveillance is every three years, every two years, and annually, respectively. In this report, the reported results with respect to further risk stratification by anti-H. pylori antibody titer in each subgroup are reviewed: (1) high-negative antibody titer subjects in Group A, representing posteradicated individuals with high risk for intestinal-type cancer; (2) high-positive antibody titer subjects in Group B, representing active inflammation with high risk for diffuse-type cancer; and (3) low-positive antibody titer subjects in Group C, representing advanced atrophy with increased risk for intestinal-type cancer. In these subjects, careful follow-up with intervals of surveillance of every three years in (1), every two years in (2), and annually in (3) should be considered.

Sa1671 Findings of Endoscopic Gastritis Vary According to the Serum Helicobacter pylori Antibody Level

Helicobacter pylori infection induces various forms of gastritis that can be diagnosed during esophagogastroduodenoscopy (EGD). This study aimed to elucidate whether the serologically identified H. pylori antibody titer is linked to functional dyspepsia (FD) subtypes and EGD findings.

False Sero-Negative Results for Helicobacter Pylori Infection Indicate Increased Risk of Severe Atrophic Gastritis in Japanese Patients

Background/objective: H. pylori infection is commonly diagnosed using an anti-H. pylori IgG antibody test. However, a proportion of results are falsely sero-negative. We investigated characteristics of patients falsely seronegative for H. pylori in relation to gastric atrophy. Methods: H. pylori infection (Hp+ or Hp-) was determined based on culture test, rapid urease test (RUT), and polymerase chain reaction (PCR) test in 280 outpatients. Anti-H. pylori antibody titers ≥ 10 U/ml were diagnosed as sero-positive for H. pylori (IgG+), while those <10 U/ml were sero-negative (IgG-). Serum pepsinogen (PG) I/PG II ratios were calculated as a serological marker of gastric atrophy. Endoscopic gastric mucosal atrophy was also assessed according to the Kimura-Takemoto classification system. Results: The mean PG I/PG II ratio in each group was as follows: Hp-/IgG- (4.99 ± 1.04, n=10), Hp+/IgG+ (2.59 ± 1.51, n=240), Hp-/IgG+ (5.65 ± 2.72, n=4) and Hp+/IgG- (3.02 ± 2.61, n=26). The mean serum PG I/PG II ratio in the Hp+/IgG- group was lower than those of Hp-/IgG- and Hp-/IgG+ groups (P=0.028 and 0.072). Incidence of severe gastric mucosal atrophy in the Hp+/IgG- group was highest of the four groups. Conclusions: Individuals falsely sero-negative for H. pylori infection is at increased risk of severe atrophic gastritis, which is well known as precancerous lesion.

Helicobacter pylori-related chronic gastritis as a risk factor for colonic neoplasms

To summarize the current views and insights on associations between Helicobacter pylori (H. pylori)-related chronic gastritis and colorectal neoplasm, we reviewed recent studies to clarify whether H. pylori infection/H. pylori-related chronic gastritis is associated with an elevated risk of colorectal neoplasm. Recent studies based on large databases with careful control for confounding variables have clearly demonstrated an increased risk of colorectal neoplasm associated with H. pylori infection. The correlation between H. pylori-related chronic atrophic gastritis (CAG) and colorectal neoplasm has only been examined in a limited number of studies. A recent large study using a national histopathological database, and our study based on the stage of H. pylori-related chronic gastritis as determined by serum levels of H. pylori antibody titer and pepsinogen, indicated that H. pylori-related CAG confers an increased risk of colorectal neoplasm, and more extensive atrophic gastritis will probably be associated with even higher risk of neoplasm. In addition, our study suggested that the activity of H. pylori-related chronic gastritis is correlated with colorectal neoplasm risk. H. pylori-related chronic gastritis could be involved in an increased risk of colorectal neoplasm that appears to be enhanced by the progression of gastric atrophy and the presence of active inflammation.

Cancer development based on chronic active gastritis and resulting gastric atrophy as assessed by serum levels of pepsinogen and Helicobacter pylori antibody titer

Our study investigated the relationship between gastric cancer development and activity of Helicobacter pylori-associated chronic gastritis or the resulting chronic atrophic gastritis (CAG). A cohort of 4,655 healthy asymptomatic subjects, in whom serum pepsinogen (PG) and H. pylori antibody titer had been measured to assess the activity and stage of H. pylori-associated chronic gastritis, was followed for up to 16 years, and cancer development was investigated. In subjects with a serologically diagnosed healthy stomach (H. pylori-negative/CAG-negative), cancer incidence rate was low, at 16/100,000 person-years. With the establishment of H. pylori infection and progression of chronic gastritis, significant stepwise cancer risk elevations were seen from CAG-free subjects (H. pylori-positive/CAG-negative) [hazard ratio (HR) = 8.9, 95% confidence interval (CI) = 2.7-54.7] to subjects with CAG (H. pylori-positive/CAG-positive) (HR = 17.7, 95% CI = 5.4-108.6) and finally to subjects with metaplastic gastritis (H. pylori-negative/CAG-positive) (HR = 69.7, 95% CI = 13.6-502.9). In H. pylori-infected CAG-free subjects, significantly elevated cancer risk was observed in the subgroup with active inflammation-based high PG II level or potent immune response-based high H. pylori antibody titer; the former was associated with a particularly high risk of diffuse-type cancer, and both subgroups showed high cancer incidence rates of around 250/100,000 person-years, comparable to that in subjects with CAG. No such risk elevation was observed in H. pylori-infected subjects with CAG. These results clearly indicate that gastric cancer develops mainly from the gastritis-atrophy-metaplasia-cancer sequence and partly from active inflammation-based direct carcinogenesis, and that serum levels of PG and H. pylori antibody titer provide indices of cancer development in H. pylori-infected subjects.

Development of an ELISA for Quantitative Detection of Immunoglobulin G (IgG) and IgA Antibodies toHelicobacter pylorifor Use in Korean Patients withH. pylori-Associated Diseases

Background/AimsWe aimed to develop a quantitative enzyme-linked immunosorbent assay (ELISA) using whole-cell lysates of Helicobacter pylori 51 and to investigate its validity.MethodsData from 300 plates were obtained by two different operators. Standard sera were used to make a standard curve to analyze the quantity of anti-H. pylori immunoglobulin G (IgG) and IgA antibody. We obtained reproducible data with fewer dilutions of samples by the addition of serially diluted standard serum to each ELISA plate. To evaluate the validity of this ELISA, the 114 H. pylori-positive and -negative subjects were stratified into four age groups, i.e., 0 to 4, 5 to 9, 10 to 15, and 20 to 29 years, before testing.ResultsThe mean IgG-antibody titers in H. pylori-positive and -negative subjects were 1,766.4 IU/mL and 654.3 IU/mL (p<0.001). The mean IgA-antibody titers in H. pylori-positive and -negative subjects were 350.1 IU/mL and 193.5 IU/mL (p<0.001). Anti-H. pylori IgG and IgA titers in the four age groups were higher in H. pylori-positive subjects than in H. pylori-negative subjects (p<0.05).ConclusionsUsing the current ELISA based on whole-cell lysates of H. pylori 51, reliable anti-H. pylori antibody titers were obtained regardless of the subject's age.

Altered mucosal DNA methylation in parallel with highly active Helicobacter pylori-related gastritis

Chronic inflammation triggered by Helicobacter pylori causes altered DNA methylation in stomach mucosae, which is deeply involved in gastric carcinogenesis. This study aimed to elucidate the correlation between altered mucosal DNA methylation levels and activity of H. pylori-related gastritis, because inflammatory activity shows particular correlations with the development of diffuse-type cancer. Methylation levels in stomach mucosae of 78 healthy volunteers were determined by real-time methylation-specific PCR or bisulfite pyrosequencing. Examined loci were the promoter CpG islands of six genes (FLNc, HAND1, THBD, p41ARC, HRASLS, and LOX) and the CpG sites of non-coding repetitive elements (Alu and Satα) that are reportedly altered by H. pylori infection. Activity of H. pylori-related gastritis was evaluated using two serum markers: H. pylori antibody titer and pepsinogen II. Methylation levels of the six CpG islands were consistently increased, and those of the two repetitive elements were consistently decreased in a stepwise manner with the activity of gastric inflammation as represented by serum marker levels. Each serum marker level was well correlated with the overall DNA methylation status of stomach mucosa, and these two serologic markers were additive in the detection of the mucosa with severely altered DNA methylation. Alteration in mucosal DNA methylation level was closely correlated with activity of H. pylori-related gastritis as evaluated by serum markers. The observed correlation between altered DNA methylation levels and activity of H. pylori-related gastritis appears to be one of the relevant molecular mechanisms underlying the development of diffuse-type cancer.

Mo1558 Evaluation of Treatment for Curatively Unresectable Gastric Cancer

Background and aims: Aberrant DNA methylation observed in the atrophic gastritis with the past infection of Helicobacter pylori (H. pylori) is associated with the risk of gastric cancer, mainly intestinal-type. In contrast, DNA methylation in gastric mucosae at risk of diffusetype gastric cancer is not fully known. We have found that the subjects with severe gastric mucosal inflammation identified by serum markers have higher risk of the development of diffuse-type gastric cancer. Thosewho showedH. pylori antibody titer >500U/mL, pepsinogen (PG) II >30 ng/mL, or PG I >70 ng/mL and PG I/II ratio 500 U/mL) and high levels of PG II (>30 ng/mL). The methylation levels were also severely altered in the subjects with serum PG I >70 ng/mL and PG I/II ratio <3.0. Conclusions: DNA methylation in gastric mucosae was closely associated with the severity of inflammation identified by serum H. pylori antibody or PGs. These results suggest that DNAmethylation works to some extent in the occurrence of diffusetype gastric cancer resulting from severe active inflammation induced by H. pylori infection.

Mo1557 DNA Methylation in Gastric Mucosae is Associated With the Severity of Mucosal Inflammation Involving the Risk of Diffuse-Type Gastric Cancer

Background and aims: Aberrant DNA methylation observed in the atrophic gastritis with the past infection of Helicobacter pylori (H. pylori) is associated with the risk of gastric cancer, mainly intestinal-type. In contrast, DNA methylation in gastric mucosae at risk of diffusetype gastric cancer is not fully known. We have found that the subjects with severe gastric mucosal inflammation identified by serum markers have higher risk of the development of diffuse-type gastric cancer. Thosewho showedH. pylori antibody titer >500U/mL, pepsinogen (PG) II >30 ng/mL, or PG I >70 ng/mL and PG I/II ratio 500 U/mL) and high levels of PG II (>30 ng/mL). The methylation levels were also severely altered in the subjects with serum PG I >70 ng/mL and PG I/II ratio <3.0. Conclusions: DNA methylation in gastric mucosae was closely associated with the severity of inflammation identified by serum H. pylori antibody or PGs. These results suggest that DNAmethylation works to some extent in the occurrence of diffusetype gastric cancer resulting from severe active inflammation induced by H. pylori infection.