Aberrant DNA Methylation in Non-Neoplastic Gastric Mucosa of H. Pylori Infected Patients and Effect of Eradication

Perri, Francesco; Cotugno, Rosa; Piepoli, Ada; Merla, Antonio; Quitadamo, M.; Gentile, Annamaria; Pilotto, Alberto; Annese, Vito; Andriulli, Angelo

doi:10.1111/j.1572-0241.2007.01284.x

Cited by 172 publications

(150 citation statements)

References 43 publications

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“…Baseline p16, CDH1, and RUNX-3 genes showed significantly higher methylation levels in H. pylori-positive patients than in H. pylori-negative normal control group. Some articles reported that patients with H. pylori had hypermethylation of p16 and CDH1 in 46-80%, while normal participants without H. pylori had no/little hypermethylation, 8,18 which was in line with our study. However, we should consider that not all patients with H. pylori infection had hypermethylation of p16 and CDH1 although hypermethylation of these genes are associated with H. pylori infection.…”

Section: Discussionsupporting

confidence: 81%

“…[7][8][9] Eradication of H. pylori might reverse methylation of these genes over the long term. We investigated methylation of the p16, CDH1, and RUNX-3 genes in gastric mucosa from patients with gastric adenoma or early gastric cancer (EGC) before and after eradication of H. pylori after one year.…”

Section: 최정민 등 헬리코박터 파일로리 치료와 유전자 과염기화mentioning

confidence: 99%

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Helicobacter pyloriEradication Modulates Aberrant CpG Island Hypermethylation in Gastric Carcinogenesis

Choi

Kim

et al. 2016

Korean J Gastroenterol

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Background/Aims: Helicobacter pylori infection induces aberrant DNA methylation in gastric mucosa. We evaluated the long-term effect of H. pylori eradication on promotor CpG island hypermethylation in gastric carcinogenesis. Methods: H. pylori-positive patients with gastric adenoma or early gastric cancer who underwent endoscopic resection were enrolled. According to H. pylori eradication after endoscopic resection, the participants were randomly assigned to H. pylori eradication or non-eradication group. H. pylori-negative gastric mucosa from normal participants provided the normal control. CpG island hypermethylation of tumor-related genes (p16, CDH1, and RUNX-3) was evaluated by quantitative MethyLight assay in non-tumorous gastric mucosa. The gene methylation rate and median values of hypermethylation were compared after one year by H. pylori status. Results: In H. pylori-positive patients, hypermethylation of p16 was found in 80.6%, of CDH1 in 80.6%, and of RUNX-3 in 48.4%. This is significantly higher than normal control (p16, 10%; CDH1, 44%; RUNX-3, 16%) (p<0.05). In the H. pylori eradication group, methylation rates of p16 and CDH1 decreased in 58.1% and 61.3% of the patients, and the median values of hypermethylation were significantly lower at one year compared with the non-eradication group. However, RUNX-3 hypermethylation did not differ significantly at one year after H. pylori eradication. The non-eradication group hypermethylation did not change after one year. Conclusions: H. pylori infection was associated with promotor hypermethylation of genes in gastric carcinogenesis, and H. pylori eradication might reverse p16 and CDH1 hypermethylation. (Korean J Gastroenterol 2016;68:253-259)

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Section: Discussionsupporting

confidence: 81%

Section: 최정민 등 헬리코박터 파일로리 치료와 유전자 과염기화mentioning

confidence: 99%

Helicobacter pyloriEradication Modulates Aberrant CpG Island Hypermethylation in Gastric Carcinogenesis

Choi

Kim

et al. 2016

Korean J Gastroenterol

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“…36 Methylation levels of protein-coding genes, including LOX, in the gastric mucosae of individuals with past infection (gastric cancer patients without H. pylori) were lower than those of individuals with current infection (both healthy volunteers and gastric cancer patients) in our previous study. 11 Actually, incidences of aberrant methylation and methylation levels of CDH1 are reported to decrease after the eradication of H. pylori, 19,37 showing that DNA methylation in gastric mucosae decreases when H. pylori infection discontinues. Interestingly, methylation levels of the three miRNA genes in the gastric mucosae of individuals with past infection by H. pylori (gastric cancer patients without H. pylori) did not decrease compared with those of individuals with current infection (healthy volunteers and gastric cancer patients).…”

Section: Discussionmentioning

confidence: 99%

“…11 In addition to gastric cancers, the presence of aberrant DNA methylation in noncancerous tissues and possible association with cancer risks have been reported for liver, 13 colon, 14 esophageal, 15 breast 16 and renal cancers. 17 Genes so far analyzed in noncancerous gastric mucosae are those methylated in gastric cancers, including tumor-suppressor genes, such as CDKN2A, MLH1, CDH1, LOX and APC, 2,11,18,19 and genes with little or no expression in normal gastric mucosae, such as FLNc, HAND1 and THBD. The latter group of genes is methylated in parallel with tumor-suppressor genes but with higher frequencies, and is considered as a good marker to detect the presence of an epigenetic field defect.…”

mentioning

confidence: 99%

DNA methylation of microRNA genes in gastric mucosae of gastric cancer patients: Its possible involvement in the formation of epigenetic field defect

Ando

Yoshida

Enomoto

et al. 2009

Intl Journal of Cancer

258

207

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Accumulation of aberrant DNA methylation in normal-appearing gastric mucosae, mostly induced by H. pylori infection, is now known to be deeply involved in predisposition to gastric cancers (epigenetic field defect), and silencing of protein-coding genes has been analyzed so far. In this study, we aimed to clarify the involvement of microRNA (miRNA) gene silencing in the field defect. First, we selected three miRNA genes as methylation-silenced after analysis of six candidate ''methylation-silenced'' tumor-suppressor miRNA genes. Methylation levels of the three genes (miR124a-1, miR-124a-2 and miR-124a-3) were quantified in 56 normal gastric mucosae of healthy volunteers (28 volunteers with H. pylori and 28 without), 45 noncancerous gastric mucosae of gastric cancer patients (29 patients with H. pylori and 16 without), and 28 gastric cancer tissues (13 intestinal and 15 diffuse types). Among the healthy volunteers, individuals with H. pylori had 7.8-13.1-fold higher methylation levels than those without (p < 0.001). Among individuals without H. pylori, noncancerous gastric mucosae of gastric cancer patients had 7.2-15.5-fold higher methylation levels than gastric mucosae of healthy volunteers (p < 0.005). Different from protein-coding genes, individuals with past H. pylori infection retained similar methylation levels to those with current infection. In cancer tissues, methylation levels were highly variable, and no difference was observed between intestinal and diffuse histological types. This strongly indicated that methylationsilencing of miRNA genes, in addition to that of protein-coding genes, contributed to the formation of a field defect for gastric cancers. ' 2008 Wiley-Liss, Inc.Key words: field for cancerization; microRNA; methylation; gastric cancer; Helicobacter pylori Metachronous occurrence of gastric cancers is becoming an important issue as localized resection of early gastric cancers by endoscopic submucosal dissection (ESD) has become common. 1 The incidence of secondary primary gastric cancers after ESD reaches as high as 2.0% per year 2 whereas the incidence of gastric cancer in the general Japanese population is 0.14% per year. 3 This indicates that noncancerous gastric mucosae are already predisposed to developing gastric cancers, forming a field defect (field for cancerization). High incidences of metachronous cancers have been known not only for gastric cancers but also for bladder, liver, and esophageal cancers 4-6 and are becoming recognized for lung, breast and colorectal cancers. [7][8][9] A molecular basis for the field defect has been considered as an accumulation of genetic and epigenetic alterations in normalappearing tissues. Traditionally, cells with a genetic alteration were considered to form a physically continuous patch, producing a genetically altered field. 10 Recently, we found that aberrant DNA methylation of specific genes can be induced in as high as several percentage of cells in noncancerous gastric mucosae (thus in multiple independent gastric glands), and the degre...

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“…Aberrant methylation of gastric mucosa genes is a common finding in humans infected with Helicobacter pylori and is an early event in gastric carcinogenesis (143)(144)(145). Insulin-like growth factor 2 methylation imprinting profile in the placenta is altered in mice infected with Campylobacter rectus during pregnancy (142).…”

Section: Infective Agents and The Epigenomementioning

confidence: 99%

Prospects for Epigenetic Epidemiology

Foley¹,

Craig²,

Morley³

et al. 2008

American Journal of Epidemiology

220

162

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Aberrant DNA Methylation in Non-Neoplastic Gastric Mucosa of H. Pylori Infected Patients and Effect of Eradication

Cited by 172 publications

References 43 publications

Helicobacter pyloriEradication Modulates Aberrant CpG Island Hypermethylation in Gastric Carcinogenesis

Helicobacter pyloriEradication Modulates Aberrant CpG Island Hypermethylation in Gastric Carcinogenesis

DNA methylation of microRNA genes in gastric mucosae of gastric cancer patients: Its possible involvement in the formation of epigenetic field defect

Prospects for Epigenetic Epidemiology

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