Risk prediction of gastric cancer by analysis of aberrant DNA methylation in non-neoplastic gastric epithelium

Tomomitsu Tahara, Tomiyasu Arisawa, Tomoyuki Shibata, Fang Yu Wang, Masakatsu Nakamura, Mikijyu Sakata, Mitsuo Nagasaka, Tamaki Takagi, Yoshio Kamiya, Hiroshi Fujita, Masahiko Nakamura, Shin Hasegawa, Masami Iwata, Kazuya Takahama, Makoto Watanabe, Ichiro Hirata, Hiroshi Nakano

研究成果: Article

39 引用 (Scopus)

抄録

Background: Aberrant DNA methylation is one of the major events in carcinogenesis. Promoter DNA methylation is also present in various non-neoplastic tissues including gastric epithelium as age-related phenomenon, suggesting that it occurs early in the process of tumorigenesis. Aim: We aimed to clarify the relationship of aberrant DNA methylation in non-neoplastic gastric epithelia with the risk of gastric cancer, Helicobactor pylori infection, and the degree of H. pylori-induced gastritis. Methods: 89 patients enrolled in this study. The status of aberrant DNA methylation was compared in two groups of patients: 43 cases with gastric cancer (mean age 65.9 years [29-91], F:M = 0.30, intestinal type [n = 25], diffuse type [n = 18]) and 46 age- and sex-matched patients without gastric cancer (peptic ulcer diseases [n = 11], gastritis [n = 35]) as a control group. Genomic DNA was extracted directly from non-neoplastic epithelia of antral biopsies obtained by endoscopy. The promoter methylation status of the p14 and p21 genes was determined by methylation-specific-polymerase chain reaction (MSP). The promoter methylation status of the p16 gene was quantified by digital densitographic analysis following MSP. The degree of gastritis in the antrum was assessed according to the updated Sydney system. The PG I/II ratio was calculated based on the data of serum PG I and PG II levels measured by radioimmunoassay. Results: In all 89 subjects, CpG island methylation was found in 25.8% for p14, 52.8% for p16, 1.1% for p21. Among non-cancer patients, the methylation frequency of the p14 gene was significantly higher in H. pylori-positive than in H. pylori-negative patients (38.5 vs. 10.0%, p = 0.03). The mean (± SD) methylation levels of the p16 gene in non-neoplastic gastric epithelium was significantly higher in gastric cancer cases both in all patients and in H. pylori-positive patients (0.45 ± 0.31 vs. 0.20 ± 0.17; p = 0.019, 0.45 ± 0.31 vs. 0.20 ± 0.17; p = 0.016, respectively). The methylation level of the p16 gene was also associated with the presence of intestinal-type gastric cancer (p = 0.017). The methylation level of the p16 gene was significantly higher in patients with intestinal metaplasia (IM) than those without (p = 0.04). Furthermore, the methylation level of the p16 gene was correlated with lower PG l/ll ratio (p = 0.04). The methylation of the p21gene was found in only 1 patient with gastric cancer. Conclusions: Our data suggest that promoter of the p14 gene may be one of the specific regions whose methylation is closely associated with H. pylori infection. Methylation levels of the p16 gene seem to be accumulated in the progression of gastric mucosal atrophy and IM, and thus may be associated with the presence of gastric cancer especially for intestinal-type histopathology.

元の言語English
ページ(範囲)54-61
ページ数8
ジャーナルDigestion
75
発行部数1
DOI
出版物ステータスPublished - 01-05-2007

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DNA Methylation
Methylation
Stomach Neoplasms
Stomach
Epithelium
p16 Genes
Pylorus
Gastritis
Metaplasia
Carcinogenesis
Intestinal Neoplasms
CpG Islands
Infection
Peptic Ulcer
Gene Frequency
Endoscopy
Genes
Atrophy
Radioimmunoassay
Biopsy

All Science Journal Classification (ASJC) codes

  • Gastroenterology

これを引用

Tahara, T., Arisawa, T., Shibata, T., Wang, F. Y., Nakamura, M., Sakata, M., ... Nakano, H. (2007). Risk prediction of gastric cancer by analysis of aberrant DNA methylation in non-neoplastic gastric epithelium. Digestion, 75(1), 54-61. https://doi.org/10.1159/000101775
Tahara, Tomomitsu ; Arisawa, Tomiyasu ; Shibata, Tomoyuki ; Wang, Fang Yu ; Nakamura, Masakatsu ; Sakata, Mikijyu ; Nagasaka, Mitsuo ; Takagi, Tamaki ; Kamiya, Yoshio ; Fujita, Hiroshi ; Nakamura, Masahiko ; Hasegawa, Shin ; Iwata, Masami ; Takahama, Kazuya ; Watanabe, Makoto ; Hirata, Ichiro ; Nakano, Hiroshi. / Risk prediction of gastric cancer by analysis of aberrant DNA methylation in non-neoplastic gastric epithelium. :: Digestion. 2007 ; 巻 75, 番号 1. pp. 54-61.
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title = "Risk prediction of gastric cancer by analysis of aberrant DNA methylation in non-neoplastic gastric epithelium",
abstract = "Background: Aberrant DNA methylation is one of the major events in carcinogenesis. Promoter DNA methylation is also present in various non-neoplastic tissues including gastric epithelium as age-related phenomenon, suggesting that it occurs early in the process of tumorigenesis. Aim: We aimed to clarify the relationship of aberrant DNA methylation in non-neoplastic gastric epithelia with the risk of gastric cancer, Helicobactor pylori infection, and the degree of H. pylori-induced gastritis. Methods: 89 patients enrolled in this study. The status of aberrant DNA methylation was compared in two groups of patients: 43 cases with gastric cancer (mean age 65.9 years [29-91], F:M = 0.30, intestinal type [n = 25], diffuse type [n = 18]) and 46 age- and sex-matched patients without gastric cancer (peptic ulcer diseases [n = 11], gastritis [n = 35]) as a control group. Genomic DNA was extracted directly from non-neoplastic epithelia of antral biopsies obtained by endoscopy. The promoter methylation status of the p14 and p21 genes was determined by methylation-specific-polymerase chain reaction (MSP). The promoter methylation status of the p16 gene was quantified by digital densitographic analysis following MSP. The degree of gastritis in the antrum was assessed according to the updated Sydney system. The PG I/II ratio was calculated based on the data of serum PG I and PG II levels measured by radioimmunoassay. Results: In all 89 subjects, CpG island methylation was found in 25.8{\%} for p14, 52.8{\%} for p16, 1.1{\%} for p21. Among non-cancer patients, the methylation frequency of the p14 gene was significantly higher in H. pylori-positive than in H. pylori-negative patients (38.5 vs. 10.0{\%}, p = 0.03). The mean (± SD) methylation levels of the p16 gene in non-neoplastic gastric epithelium was significantly higher in gastric cancer cases both in all patients and in H. pylori-positive patients (0.45 ± 0.31 vs. 0.20 ± 0.17; p = 0.019, 0.45 ± 0.31 vs. 0.20 ± 0.17; p = 0.016, respectively). The methylation level of the p16 gene was also associated with the presence of intestinal-type gastric cancer (p = 0.017). The methylation level of the p16 gene was significantly higher in patients with intestinal metaplasia (IM) than those without (p = 0.04). Furthermore, the methylation level of the p16 gene was correlated with lower PG l/ll ratio (p = 0.04). The methylation of the p21gene was found in only 1 patient with gastric cancer. Conclusions: Our data suggest that promoter of the p14 gene may be one of the specific regions whose methylation is closely associated with H. pylori infection. Methylation levels of the p16 gene seem to be accumulated in the progression of gastric mucosal atrophy and IM, and thus may be associated with the presence of gastric cancer especially for intestinal-type histopathology.",
author = "Tomomitsu Tahara and Tomiyasu Arisawa and Tomoyuki Shibata and Wang, {Fang Yu} and Masakatsu Nakamura and Mikijyu Sakata and Mitsuo Nagasaka and Tamaki Takagi and Yoshio Kamiya and Hiroshi Fujita and Masahiko Nakamura and Shin Hasegawa and Masami Iwata and Kazuya Takahama and Makoto Watanabe and Ichiro Hirata and Hiroshi Nakano",
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doi = "10.1159/000101775",
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Tahara, T, Arisawa, T, Shibata, T, Wang, FY, Nakamura, M, Sakata, M, Nagasaka, M, Takagi, T, Kamiya, Y, Fujita, H, Nakamura, M, Hasegawa, S, Iwata, M, Takahama, K, Watanabe, M, Hirata, I & Nakano, H 2007, 'Risk prediction of gastric cancer by analysis of aberrant DNA methylation in non-neoplastic gastric epithelium', Digestion, 巻. 75, 番号 1, pp. 54-61. https://doi.org/10.1159/000101775

Risk prediction of gastric cancer by analysis of aberrant DNA methylation in non-neoplastic gastric epithelium. / Tahara, Tomomitsu; Arisawa, Tomiyasu; Shibata, Tomoyuki; Wang, Fang Yu; Nakamura, Masakatsu; Sakata, Mikijyu; Nagasaka, Mitsuo; Takagi, Tamaki; Kamiya, Yoshio; Fujita, Hiroshi; Nakamura, Masahiko; Hasegawa, Shin; Iwata, Masami; Takahama, Kazuya; Watanabe, Makoto; Hirata, Ichiro; Nakano, Hiroshi.

:: Digestion, 巻 75, 番号 1, 01.05.2007, p. 54-61.

研究成果: Article

TY - JOUR

T1 - Risk prediction of gastric cancer by analysis of aberrant DNA methylation in non-neoplastic gastric epithelium

AU - Tahara, Tomomitsu

AU - Arisawa, Tomiyasu

AU - Shibata, Tomoyuki

AU - Wang, Fang Yu

AU - Nakamura, Masakatsu

AU - Sakata, Mikijyu

AU - Nagasaka, Mitsuo

AU - Takagi, Tamaki

AU - Kamiya, Yoshio

AU - Fujita, Hiroshi

AU - Nakamura, Masahiko

AU - Hasegawa, Shin

AU - Iwata, Masami

AU - Takahama, Kazuya

AU - Watanabe, Makoto

AU - Hirata, Ichiro

AU - Nakano, Hiroshi

PY - 2007/5/1

Y1 - 2007/5/1

N2 - Background: Aberrant DNA methylation is one of the major events in carcinogenesis. Promoter DNA methylation is also present in various non-neoplastic tissues including gastric epithelium as age-related phenomenon, suggesting that it occurs early in the process of tumorigenesis. Aim: We aimed to clarify the relationship of aberrant DNA methylation in non-neoplastic gastric epithelia with the risk of gastric cancer, Helicobactor pylori infection, and the degree of H. pylori-induced gastritis. Methods: 89 patients enrolled in this study. The status of aberrant DNA methylation was compared in two groups of patients: 43 cases with gastric cancer (mean age 65.9 years [29-91], F:M = 0.30, intestinal type [n = 25], diffuse type [n = 18]) and 46 age- and sex-matched patients without gastric cancer (peptic ulcer diseases [n = 11], gastritis [n = 35]) as a control group. Genomic DNA was extracted directly from non-neoplastic epithelia of antral biopsies obtained by endoscopy. The promoter methylation status of the p14 and p21 genes was determined by methylation-specific-polymerase chain reaction (MSP). The promoter methylation status of the p16 gene was quantified by digital densitographic analysis following MSP. The degree of gastritis in the antrum was assessed according to the updated Sydney system. The PG I/II ratio was calculated based on the data of serum PG I and PG II levels measured by radioimmunoassay. Results: In all 89 subjects, CpG island methylation was found in 25.8% for p14, 52.8% for p16, 1.1% for p21. Among non-cancer patients, the methylation frequency of the p14 gene was significantly higher in H. pylori-positive than in H. pylori-negative patients (38.5 vs. 10.0%, p = 0.03). The mean (± SD) methylation levels of the p16 gene in non-neoplastic gastric epithelium was significantly higher in gastric cancer cases both in all patients and in H. pylori-positive patients (0.45 ± 0.31 vs. 0.20 ± 0.17; p = 0.019, 0.45 ± 0.31 vs. 0.20 ± 0.17; p = 0.016, respectively). The methylation level of the p16 gene was also associated with the presence of intestinal-type gastric cancer (p = 0.017). The methylation level of the p16 gene was significantly higher in patients with intestinal metaplasia (IM) than those without (p = 0.04). Furthermore, the methylation level of the p16 gene was correlated with lower PG l/ll ratio (p = 0.04). The methylation of the p21gene was found in only 1 patient with gastric cancer. Conclusions: Our data suggest that promoter of the p14 gene may be one of the specific regions whose methylation is closely associated with H. pylori infection. Methylation levels of the p16 gene seem to be accumulated in the progression of gastric mucosal atrophy and IM, and thus may be associated with the presence of gastric cancer especially for intestinal-type histopathology.

AB - Background: Aberrant DNA methylation is one of the major events in carcinogenesis. Promoter DNA methylation is also present in various non-neoplastic tissues including gastric epithelium as age-related phenomenon, suggesting that it occurs early in the process of tumorigenesis. Aim: We aimed to clarify the relationship of aberrant DNA methylation in non-neoplastic gastric epithelia with the risk of gastric cancer, Helicobactor pylori infection, and the degree of H. pylori-induced gastritis. Methods: 89 patients enrolled in this study. The status of aberrant DNA methylation was compared in two groups of patients: 43 cases with gastric cancer (mean age 65.9 years [29-91], F:M = 0.30, intestinal type [n = 25], diffuse type [n = 18]) and 46 age- and sex-matched patients without gastric cancer (peptic ulcer diseases [n = 11], gastritis [n = 35]) as a control group. Genomic DNA was extracted directly from non-neoplastic epithelia of antral biopsies obtained by endoscopy. The promoter methylation status of the p14 and p21 genes was determined by methylation-specific-polymerase chain reaction (MSP). The promoter methylation status of the p16 gene was quantified by digital densitographic analysis following MSP. The degree of gastritis in the antrum was assessed according to the updated Sydney system. The PG I/II ratio was calculated based on the data of serum PG I and PG II levels measured by radioimmunoassay. Results: In all 89 subjects, CpG island methylation was found in 25.8% for p14, 52.8% for p16, 1.1% for p21. Among non-cancer patients, the methylation frequency of the p14 gene was significantly higher in H. pylori-positive than in H. pylori-negative patients (38.5 vs. 10.0%, p = 0.03). The mean (± SD) methylation levels of the p16 gene in non-neoplastic gastric epithelium was significantly higher in gastric cancer cases both in all patients and in H. pylori-positive patients (0.45 ± 0.31 vs. 0.20 ± 0.17; p = 0.019, 0.45 ± 0.31 vs. 0.20 ± 0.17; p = 0.016, respectively). The methylation level of the p16 gene was also associated with the presence of intestinal-type gastric cancer (p = 0.017). The methylation level of the p16 gene was significantly higher in patients with intestinal metaplasia (IM) than those without (p = 0.04). Furthermore, the methylation level of the p16 gene was correlated with lower PG l/ll ratio (p = 0.04). The methylation of the p21gene was found in only 1 patient with gastric cancer. Conclusions: Our data suggest that promoter of the p14 gene may be one of the specific regions whose methylation is closely associated with H. pylori infection. Methylation levels of the p16 gene seem to be accumulated in the progression of gastric mucosal atrophy and IM, and thus may be associated with the presence of gastric cancer especially for intestinal-type histopathology.

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