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 infection induces chronic inflammation and is the strongest known risk factor for gastric cancer. The genomes of H pylori are highly diverse and therefore bacterial virulence factors play an important role in determining the outcome of H pylori infection, in combination with host responses that are augmented by environmental and dietary risk factors. It is important to gain further understanding of the pathogenesis of H pylori infection to develop more effective treatments for this common but deadly malignancy. This review focuses on the specific mechanisms used by H pylori to drive gastric carcinogenesis.Gastroenterology clinics of North America 06/2013; 42(2):285-98. · 2.56 Impact Factor
Article: Gene methylation in gastric cancer.[show abstract] [hide abstract]
ABSTRACT: Gastric cancer is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide. Over 70% of new cases and deaths occur in developing countries. In the early years of the molecular biology revolution, cancer research mainly focuses on genetic alterations, including gastric cancer. Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns in mammals. Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation. Recent advancements in the rapidly evolving field of cancer epigenetics have shown extensive reprogramming of every component of the epigenetic machinery in cancer, including DNA methylation, histone modifications, nucleosome positioning, noncoding RNAs, and microRNAs. Aberrant DNA methylation in the promoter regions of gene, which leads to inactivation of tumor suppressor and other cancer-related genes in cancer cells, is the most well-defined epigenetic hallmark in gastric cancer. The advantages of gene methylation as a target for detection and diagnosis of cancer in biopsy specimens and non-invasive body fluids such as serum and gastric washes has led to many studies of application in gastric cancer. This review focuses on the most common and important phenomenon of epigenetics, DNA methylation, in gastric cancer and illustrates the impact epigenetics has had on this field.Clinica chimica acta; international journal of clinical chemistry 05/2013; · 2.54 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