Increased number of methylated CpG islands correlates with Helicobacter pylori infection, histological and serological severity of chronic gastritis

Tahara, Tomomitsu; Arisawa, Tomiyasu; Shibata, Tomoyuki; Nakamura, Masakatsu; Yoshioka, Daisuke; Okubo, Masaaki; Maruyama, Naoko; Kamano, Toshiaki; Kamiya, Yoshio; Fujita, Hiroshi; Nakagawa, Yoshihito; Nagasaka, Mitsuo; Iwata, Masami; Takahama, Kazuya; Watanabe, Makoto; Yamashita, Hiromi; Hirata, Ichiro

doi:10.1097/meg.0b013e32830e28b2

Cited by 35 publications

(100 citation statements)

References 16 publications

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“…All the subjects underwent upper gastroscopy as part of a health check, as a secondary procedure following barium X-ray examination for suspected stomach cancer, or for the investigation of abdominal discomfort. This cohort was partly recruited from recent study investigating the association between promoter CIHM and severity of chronic gastritis (12), host genetic factors (31). Patients who had severe systemic disease, or malignancy in the stomach or other organ, who had a history of gastric surgery were excluded from the study.…”

Section: Methodsmentioning

confidence: 99%

“…Methylation of DAP-kinase has been reported in many cancers (8) including gastric cancer (9,10). It has also been reported that CIHM of those 4 genes are frequently occurred in non-cancerous gastric mucosa in relation to H. pylori infection (7,11,12), histological or serological severity of gastritis (12) and gastric cancer occurrence (13)(14)(15). Therefore, they may be susceptible candidate genes for CIHM in the stomach.…”

Section: Introductionmentioning

confidence: 98%

“…One of the most important factors causing CIHM in the stomach is H. pylori infection (7,11,12), which induces chronic inflammation, causing oxidative stress to the gastric epithelium (16,17). However, there is considerable variation in the extent of gastric inflammation among H. pylori infected patients and not all of them show same CIHM status, suggesting that some inter individual genetic difference may contribute to this process.…”

Section: Introductionmentioning

confidence: 99%

“…In this study, we investigated the prevalence of CIHM of 4 candidate genes: p14, p16, CDH1 and DAP-kinase, they have been thought to be most susceptible for methylation in the stomach (7,(11)(12)(13)(14)(15) among non-cancerous gastric mucosa and its relation to IL-17A, IL-17F and MIF polymorphisms.…”

Section: Introductionmentioning

confidence: 99%

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Effect of polymorphisms of IL-17A, -17F and MIF genes on CpG island hyper-methylation (CIHM) in the human gastric mucosa

et al. 2009

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Abstract. CpG island hyper-methylation (CIHM) is one of the major events in the gastric carcinogenesis and also occurs in non-neoplastic gastric mucosa. IL-17A, -17F and MIF have a crucial role in the gastric inflammationand carcinogenesis. The CIHM status in the non-cancerous gastric mucosa, in relation to IL-17A (-197G>A, rs2275913), -17F (7488T>C, rs763780) and MIF (-173G>C and -794 tetranucleotide repeats) polymorphisms was investigated. Gastric mucosa samples were obtained from 121 cancer free subjects. CIHM of p14, p16, DAP-kinase and CDH1 genes were determined by methylation-specific polymerase chain reaction (MSP). CIHM high was defined as three or all CpG islands methylated. We employed the PCR-SSCP (multiplex PCR for IL-17A and -17F) method to detect the gene polymorphisms. No association were found between CIHM status and L-17A (-197G>A), IL-17F (7488T>C) and MIF (-173G>C) polymorphisms. MIF 5-CATT repeat carrier (5/5+5/6+5/7) held a significantly higher risk of CIHM of DAP-kinase (OR=2.33, 95% CI=1.07-5.09, p=0.03) and CIHM high (OR=3.63, 95% CI=1.31-10.08, p=0.01). Weak association was also found between the same genotype and increased risk of CIHM of p16 (OR=2.45, 95% CI=0. 90-6.68, p=0.08) and CDH1 (OR=2.23, 95% CI=0.94-5.32, p=0.07). 6-CATT repeat carrier (5/6+6/6+6/7) was significantly associated with reduced risk of CIHM of p16 (OR=0.31, 95% CI=0.11-0.90, p=0.03), CDH1 (OR=0.40, 95% CI=0.17-0.98, p=0.045), DAP-kinase (OR=0.37, 95% CI=0.17-0.83, p=0.02) and CIHM high (OR=0.25, 95% CI=0.09-0.74, p=0.01). -7-CATT repeat carrier (6/7+7/7) was weakly associated with reduced risk of CIHM of p16 (OR=0.34, 95% CI=0.10-1.13, p=0.08), DAP-kinase (OR=0.43, 95% CI=0.17-1.06, p=0.07) and CIHM high (OR=0.38, 95% CI=0.12-1.20, p=0.098). The present results provided the first evidence that the genetic polymorphisms MIF polymorphism is associated with CIHM status in the human gastric mucosa. Genetic polymorphisms of MIF-794-CATT repeat may be involved in methylation related carcinogenesis in the stomach.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of polymorphisms of IL-17A, -17F and MIF genes on CpG island hyper-methylation (CIHM) in the human gastric mucosa

et al. 2009

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“…Rates of hypermethylation were variable, ranging from 30% to 82%. 8,19 In addition, some studies reported that methylation of MLH1 and MGMT did not decrease significantly after H. pylori eradication. 8,20 Conversely, a recent study showed that MGMT methylation was significantly reduced after H. pylori eradication in patients with H. pylori gastritis (from 70% to 48%).…”

Section: Discussionmentioning

confidence: 99%

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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Effect of polymorphisms of IL‐1β and TNF‐α genes on CpG island hyper methylation (CIHM) in the nonneoplastic gastric mucosa

Tahara

Shibata

Nakamura

et al. 2011

Molecular Carcinogenesis

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CpG island hyper methylation (CIHM) is one of the major events in gastric carcinogenesis. To evaluate the influence of host genetic factors in CIHM related carcinogenesis, we investigated the association between common polymorphisms in IL-1β and TNF-α genes, with CIHM status in the nonneoplastic gastric mucosa. Polymorphisms in the IL-1β gene (-31T>C and -511C>T) and the TNF-α gene (-857C>T) were genotyped in 385 cancer-free subjects. CIHM of four candidate genes: p16 (INK4a), p14 (ARF), E-cadherin (CDH1), and death-associated protein kinase (DAP-kinase), were determined by methylation-specific-polymerase chain reaction (MSP). CIHM high was defined as two or more CpG islands methylated. CIHM of all four genes and CIHM high were significantly associated with Helicobacter pylori infection status. In over all, significant marginal association was found between IL-1β-511 TT genotype and reduced susceptibility to CIHM of DAP-kinase (adjusted OR = 0.48, 95% CI = 0.29-0.78) and CIHM high (adjusted OR = 0.53, 95% CI = 0.32-0.86). This association was more enhanced in subjects 65 yr or younger age. We also found positive association between TNF-α-857T carrier and increased susceptibility to CIHM of CDH (adjusted OR = 1.78, 95% CI = 1.01-3.16), and CIHM high (adjusted OR = 1.86, 95% CI = 1.04-3.33) in the same generation. The mean number of CIHM was lower in subjects with IL-1β-511TT genotype, while the mean number was higher in subjects with TNF-α-857 T carrier especially in subjects 65 yr and younger patients. IL-1β-511 TT genotype is associated with reduced susceptibility to CIHM especially in younger generation. Furthermore, the TNF-α-857T carrier is associated with increased susceptibility of CIHM in the same generation.

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Increased number of methylated CpG islands correlates with Helicobacter pylori infection, histological and serological severity of chronic gastritis

Abstract: Multiple promoter CpG islands would be methylated by H. pylori infection, and an increased number of methylated CpG sites correlate with histological and serological severity of chronic gastritis.

Cited by 35 publications

References 16 publications

Effect of polymorphisms of IL-17A, -17F and MIF genes on CpG island hyper-methylation (CIHM) in the human gastric mucosa

Effect of polymorphisms of IL-17A, -17F and MIF genes on CpG island hyper-methylation (CIHM) in the human gastric mucosa

Helicobacter pyloriEradication Modulates Aberrant CpG Island Hypermethylation in Gastric Carcinogenesis

Effect of polymorphisms of IL‐1β and TNF‐α genes on CpG island hyper methylation (CIHM) in the nonneoplastic gastric mucosa

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