scholarly journals Long-term Changes In Aberrant DNA Methylation And Gastritis After Helicobacter Pylori Eradication Focused On Metachronous Gastric Cancer

2021 ◽  
Author(s):  
Ikko Tanaka ◽  
Shoko Ono ◽  
Yoshiyuki Watanabe ◽  
Hiroyuki Yamamoto ◽  
Ritsuko Oikawa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Dna Methylation ◽  
Helicobacter Pylori ◽  
Methylation Level ◽  
Aberrant Methylation ◽  
Long Term Changes ◽  
Metachronous Gastric Cancer ◽  
Aberrant Dna Methylation ◽  
H Pylori

Abstract BackgroundA persistently high methylation level in gastric mucosa after Helicobacter pylori (H. pylori) eradication is presumed to be a risk for metachronous gastric cancer (MGC); however, long-term changes in aberrant DNA methylation and histological gastritis have been unclear. Our aim was to examine changes in DNA methylation and histological gastritis according to the occurrence of MGC.MethodsSubjects were classified into 3 groups: 25 patients in whom metachronous gastric cancers occurred after the initial endoscopic resection (ER) for early gastric cancer and H. pylori eradication (MGC group), 17 patients in whom MGC did not occur for more than 5 years after initial ER and H. pylori eradication (non-MGC group) and 29 patients without a history of gastric cancer who succeeded in eradication more than 5 years ago (HP group). Aberrance of DNA methylation in 3 genes (miR-124a-3, EMX1, NKX6-1) and histological score of atrophy and intestinal metaplasia (IM) were evaluated using biopsy samples before and more than a mean of 5 years after H. pylori eradication.ResultsThe methylation level of miR-124a-3 in the HP group and non-MGC group and that of EMX1 in the HP group significantly decreased in the long term after eradication. In the MGC group, H. pylori eradication did not improve aberrant methylation, and the Z-score significantly increased. There were significant positive correlations between methylation levels in miR-124a-3 and EMX1 and histological findings after eradication.ConclusionsA persistently high methylation level after H. pylori eradication reflected precancerous mucosal conditions and led to long-term MGC.

scholarly journals DNA Methylation Silencing of microRNA Gene Methylater in the Precancerous Background Mucosa with and without Gastric Cancer: Analysis of Effects of Helicobacter pylori Eradication and Long-Term Aspirin Use

2019 ◽  
Author(s):  
Jiro Watari ◽  
Chiyomi Ito ◽  
Tadakazu Shimoda ◽  
Toshihiko Tomita ◽  
Tadayuki Oshima ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Dna Methylation ◽  
Helicobacter Pylori ◽  
Early Stage ◽  
Surrogate Marker ◽  
Predictive Marker ◽  
Microrna Gene ◽  
H Pylori ◽  
Background Mucosa

The risk of gastric cancer (GC) declines after Helicobacter pylori (H. pylori) eradication and long-term aspirin use. We evaluated the effects of H. pylori eradication (Cohort 1) and aspirin use (Cohort 2) on the methylation of microRNAs (miRNAs) such as miR-34c, miR-124a-3, miR-129-2, and miR-137 in the gastric mucosa with and without GC, i.e., atrophic mucosa (AM) and intestinal metaplasia (IM). DNA was isolated from AM and IM separately using laser caption microdissection. In Cohort 1, H. pylori eradication was associated with a significant reduction of miR-124a-3 methylation only in AM, but not in IM. miR-129-2 methylation in AM may be a surrogate marker of GC in H. pylori-infected patients. In Cohort 2, aspirin did not reverse miRNA methylation in either AM or IM irrespective of H. pylori infection. miR-129-2 methylation in AM was an independent predictive marker of GC in H. pylori-infected but not -eradicated patients. These results indicate that H. pylori eradication and aspirin use were less effective in improving methylation in IM compared with AM; thus, these interventions are recommended at an early stage prior to the development of IM to prevent GC development.

scholarly journals Discovery and Validation of Novel Methylation Markers in Helicobacter pylori-Associated Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Huan Wang ◽  
Nian-Shuang Li ◽  
Cong He ◽  
Chuan Xie ◽  
Yin Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Dna Methylation ◽  
Helicobacter Pylori ◽  
Gene Expression Data ◽  
Functional Enrichment ◽  
Expression Data ◽  
H Pylori

Previous studies have shown that abnormal methylation is an early key event in the pathogenesis of most human cancers, contributing to the development of tumors. However, little attention has been given to the potential of DNA methylation patterns as markers for Helicobacter pylori- (H. pylori-) associated gastric cancer (GC). In this study, an integrated analysis of DNA methylation and gene expression was conducted to identify some potential key epigenetic markers in H. pylori-associated GC. DNA methylation data of 28 H. pylori-positive and 168 H. pylori-negative GC samples were compared and analyzed. We also analyzed the gene expression data of 18 H. pylori-positive and 145 H. pylori-negative GC cases. Finally, the results were verified by in vitro and in vivo experiments. A total of 5609 differentially methylated regions associated with 2454 differentially methylated genes were identified. A total of 228 differentially expressed genes were identified from the gene expression data of H. pylori-positive and H. pylori-negative GC cases. The screened genes were analyzed for functional enrichment. Subsequently, we obtained 28 genes regulated by methylation through a Venn diagram, and we identified five genes (GSTO2, HUS1, INTS1, TMEM184A, and TMEM190) downregulated by hypermethylation. HUS1, GSTO2, and TMEM190 were expressed at lower levels in GC than in adjacent samples ( P < 0.05 ). Moreover, H. pylori infection decreased HUS1, GSTO2, and TMEM190 expression in vitro and in vivo. Our study identified HUS1, GSTO2, and TMEM190 as novel methylation markers for H. pylori-associated GC.

scholarly journals Mass eradication of Helicobacter pylori to reduce gastric cancer incidence and mortality: a long-term cohort study on Matsu Islands

Gut ◽  
2020 ◽  
pp. gutjnl-2020-322200 ◽  
Author(s):  
Tsung-Hsien Chiang ◽  
Wei-Jung Chang ◽  
Sam Li-Sheng Chen ◽  
Amy Ming-Fang Yen ◽  
Jean Ching-Yuan Fann ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Cancer Incidence ◽  
Control Period ◽  
Eradication Therapy ◽  
Incidence Rates ◽  
Long Term Effects ◽  
Incidence And Mortality ◽  
H Pylori

ObjectiveAlthough mass eradication of Helicobacter pylori has been proposed as a means to eliminate gastric cancer, its long-term effects remain unclear.DesignMass eradication of H. pylori infection was launched in 2004 and continued until 2018 for a high-risk Taiwanese population aged 30 years or older dwelling on Matsu Islands with prevalent H. pylori infection. Test positives for the 13C-urea breath test underwent eradication therapy. We evaluated the effectiveness of the mass eradication in reducing two main outcomes, incidence and mortality rates of gastric cancer, until the end of 2016 and 2018, respectively.ResultsAfter six rounds of mass screening and eradication, the coverage rate reached 85.5% (6512/7616). The referral rate for treatment was 93.5% (4286/4584). The prevalence rates of H. pylori fell from 64.2% to 15.0% with reinfection rates of less than 1% per person-year. The presence and severity of atrophic gastritis and intestinal metaplasia also decreased with time. Compared with the historical control period from 1995 to 2003, the effectiveness in reducing gastric cancer incidence and mortality during the chemoprevention period was 53% (95% CI 30% to 69%, p<0.001) and 25% (95% CI −14% to 51%, p=0.18), respectively. No significant changes were noted in the incidence rates of other digestive tract cancers or the antibiotic resistance rate of H. pylori.ConclusionPopulation-based eradication of H. pylori has significantly reduced gastric cancer incidence with no increase in the likelihood of adverse consequences. A significant reduction in mortality is likely to be achieved with a longer follow-up period.Trial registration numberNCT00155389

Weniger metachrone Tumoren nach H.-pylori-Eradikation

2019 ◽  
Vol 51 (01) ◽  
pp. 33-36
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Metachronous Gastric Cancer ◽  
H Pylori

Choi IJ et al. Helicobacter pylori therapy for the prevention of metachronous gastric cancer. N Engl J Med 2018; 378: 1085–1095

scholarly journals Helicobacter pylori Eradication in Patients Undergoing Gastrectomy: Diagnosis and Therapy

2020 ◽  
Vol 20 (3) ◽  
pp. 204-209
Author(s):  
Youn I Choi ◽  
Jun-Won Chung
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Diagnostic Tests ◽  
Remnant Stomach ◽  
Optimal Timing ◽  
Helicobacter Pylori Eradication ◽  
Metachronous Gastric Cancer ◽  
H Pylori

The role of <i>Helicobacter pylori</i> (<i>H. pylori</i>) eradication in patients undergoing gastrectomy for gastric cancer is unclear. Although European and Asian guidelines strongly recommend <i>H. pylori</i> eradication in patients who undergo endoscopic resection for early gastric cancer, these guidelines do not specify the tests useful for diagnosing <i>H. pylori</i> infection, the optimal timing and appropriate eradication regimens, and follow-up strategies in patients undergoing gastrectomy for gastric cancer. This review aims to update the guidelines for the diagnosis and management of <i>H. pylori</i> infection in patients undergoing gastrectomy for gastric cancer. We have focused on the following issues: 1) diagnostic tests for <i>H. pylori</i> infection in the remnant stomach, 2) optimal timing and regimen for <i>H. pylori</i> eradication, and 3) role of <i>H. pylori</i> eradication in reducing the risk of metachronous gastric cancer in the remnant stomach.

scholarly journals Helicobacter pylori Infection following Endoscopic Resection of Early Gastric Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Lan Li ◽  
Chaohui Yu
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Early Gastric Cancer ◽  
Endoscopic Resection ◽  
Precancerous Lesions ◽  
Cost Effective ◽  
Reduce Healthcare Cost ◽  
Metachronous Gastric Cancer ◽  
H Pylori ◽  
Meta Analyses

The role of Helicobacter pylori (H. pylori) infection in patients following endoscopic resection of early gastric cancer (EGC) remains unclear. This article presents a review of literature published in the past 15 years. H. pylori‐mediated persistent methylation levels are associated with the development of metachronous gastric cancer. The methylation of certain specific genes can be used to identify patients with a high risk of metachronous gastric cancer even after H. pylori eradication. H. pylori eradication after endoscopic resection should be performed as early as possible for eradication success and prevention of metachronous precancerous lesions. Although whether the eradication of H. pylori could prevent the development of metachronous cancer after endoscopic resection is controversial, several meta‐analyses concluded that H. pylori eradication could reduce the incidence of metachronous gastric cancer significantly. In addition, H. pylori eradication in gastric cancer survivors after endoscopic resection could reduce healthcare cost and save lives in a cost‐effective way. Taken together, H. pylori eradication after endoscopic resection of EGC is recommended as prevention for metachronous precancerous lesions and metachronous gastric cancer.

scholarly journals Follow-Up Study Confirms the Presence of Gastric Cancer DNA Methylation Hallmarks in High-Risk Precursor Lesions

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2760
Author(s):  
Antonio Gómez ◽  
Miguel L. Pato ◽  
Luis Bujanda ◽  
Núria Sala ◽  
Osmel Companioni ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Dna Methylation ◽  
Intestinal Metaplasia ◽  
Risk Scores ◽  
Aberrant Methylation ◽  
Precursor Lesions ◽  
Genome Wide ◽  
H Pylori ◽  
Late Stages

To adopt prevention strategies in gastric cancer, it is imperative to develop robust biomarkers with acceptable costs and feasibility in clinical practice to stratified populations according to risk scores. With this aim, we applied an unbiased genome-wide CpG methylation approach to a discovery cohort composed of gastric cancer (n = 24), and non-malignant precursor lesions (n = 64). Then, candidate-methylation approaches were performed in a validation cohort of precursor lesions obtained from an observational longitudinal study (n = 264), with a 12-year follow-up to identify repression or progression cases. H. pylori stratification and histology were considered to determine their influence on the methylation dynamics. As a result, we ascertained that intestinal metaplasia partially recapitulates patterns of aberrant methylation of intestinal type of gastric cancer, independently of the H. pylori status. Two epigenetically regulated genes in cancer, RPRM and ZNF793, consistently showed increased methylation in intestinal metaplasia with respect to earlier precursor lesions. In summary, our result supports the need to investigate the practical utilities of the quantification of DNA methylation in candidate genes as a marker for disease progression. In addition, the H. pylori-dependent methylation in intestinal metaplasia suggests that pharmacological treatments aimed at H. pylori eradication in the late stages of precursor lesions do not prevent epigenome reprogramming toward a cancer signature.

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