Effects of Helicobacter pylori eradication on methylation status of E-cadherin gene in noncancerous stomach.
ABSTRACT Promoter hypermethylation of E-cadherin plays an important role on gastric cancer development. Whereas E-cadherin methylation was frequently detected in the stomach of Helicobacter pylori-infected individuals, we tested whether eradication of H. pylori alters the methylation status of the noncancerous gastric epithelium.
Endoscopic biopsies were taken from the antrum and corpus of H. pylori-infected subjects without gastric cancer. Presence of methylated E-cadherin sequences in the gastric specimens was detected by methylation-specific PCR. Bisulfite DNA sequencing was done to determine the topographical distribution and changes in methylation profiles with H. pylori eradication.
Among the 28 H. pylori-infected subjects (median age, 44.5 years), 15 (53.6%) had E-cadherin methylation detected in stomach at baseline. Discordant methylation patterns between the antrum and corpus were noted in six patients. One year after successful H. pylori eradication, there was a significant reduction in the methylation density of the promoter region and exon 1 of the E-cadherin gene as detected by bisulfite DNA sequencing (P < 0.001).
Promoter methylation in E-cadherin was frequently detected in the stomach of H. pylori-infected individuals. Eradication of H. pylori might possibly reduce the methylation density in E-cadherin gene and the chance of subsequent neoplastic transformation.
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ABSTRACT: Helicobacter pylori (H. pylori) infection is well known to be associated with the development of precancerous lesions such as chronic atrophic gastritis (AG), or gastric intestinal metaplasia (GIM), and cancer. Various molecular alterations are identified not only in gastric cancer (GC) but also in precancerous lesions. H. pylori treatment seems to improve AG and GIM, but still remains controversial. In contrast, many studies, including meta-analysis, show that H. pylori eradication reduces GC. Molecular markers detected by genetic and epigenetic alterations related to carcinogenesis reverse following H. pylori eradication. This indicates that these changes may be an important factor in the identification of high risk patients for cancer development. Patients who underwent endoscopic treatment of GC are at high risk for development of metachronous GC. A randomized controlled trial from Japan concluded that prophylactic eradication of H. pylori after endoscopic resection should be used to prevent the development of metachronous GC, but recent retrospective studies did not show the tendency. Patients with precancerous lesions (molecular alterations) that do not reverse after H. pylori treatment, represent the "point of no return" and may be at high risk for the development of GC. Therefore, earlier H. pylori eradication should be considered for preventing GC development prior to the appearance of precancerous lesions.World Journal of Gastroenterology 05/2014; 20(18):5461-5473. · 2.55 Impact Factor
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ABSTRACT: Gastric cancer is believed to result in part from the accumulation of multiple genetic and epigenetic alterations leading to oncogene overexpression and tumor suppressor loss. Tumor suppressor genes are inactivated more frequently by promoter methylation than by mutation in gastric cancer. Identification of genes inactivated by promoter methylation is a powerful approach to discover novel tumor suppressor genes. We have previously identified tumor suppressor genes in gastric cancer by genome-wide methylation screening. The biological functions of these genes are related to cell adhesion, ubiquitination, transcription, p53 regulation and diverse signaling pathways. Some of the tumor suppressor genes are of particular clinical importance as they can be used as predictive biomarkers for early diagnosis or ongoing prognosis of gastric cancer.Expert Review of Molecular Diagnostics 06/2013; 13(5):445-55. · 4.09 Impact Factor
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ABSTRACT: Remarkable progress in the field of epigenetics has turned academic, medical and public attention to the potential applications of these new advances in medicine and biomedical research. The result is a broader appreciation of epigenetic phenomena in the etiology of common human diseases, notably cancer. These advances represent an exciting opportunity to incorporate epigenetics and epigenomics into carcinogen identification and safety assessment. Current epigenetic studies, including major international sequencing projects, should generate information establishing the "normal" epigenome of tissues and cell types as well as the physiological variability of the epigenome against which carcinogen exposure can be assessed. Despite epigenetic events emerging as key mechanisms in cancer development, our search of the Monograph Volume 100 revealed that the use of epigenetic data in evaluating human carcinogens by the International Agency for Research on Cancer (IARC) Monographs has been modest so far. Here, we review (i) the current status of epigenetics incorporation in carcinogen evaluation in the IARC Monographs Programme, (ii) potential modes of action for epigenetic carcinogens, (iii) current in vivo and in vitro technologies to detect epigenetic carcinogens, (iv) genomic regions and epigenetic modifications and their biological consequences, (v) critical technological and biological issues in assessing epigenetic carcinogens. We also discuss issues related to opportunities and challenges in applying epigenetic testing in carcinogen identification and evaluation. Although epigenetic assays are just beginning to be applied in carcinogen evaluation, important data are being generated and valuable scientific resources are being established that should catalyze future applications of epigenetic testing.Carcinogenesis 06/2013; · 5.64 Impact Factor