Prostate stem cell antigen gene polymorphism is associated with H. Pylori–related promoter DNA methylation in nonneoplastic gastric epithelium

Tomomitsu Tahara, Sayumi Tahara, Noriyuki Horiguchi, Takema Kato, Yasuko Shinkai, Masaaki Okubo, Tsuyoshi Terada, Dai Yoshida, Kohei Funasaka, Mitsuo Nagasaka, Yoshihito Nakagawa, Hiroki Kurahashi, Tomoyuki Shibata, Tetsuya Tsukamoto, Naoki Omiya

Research output: Contribution to journalArticle

Abstract

Genome-wide association study identified two functional SNPs associated with gastric cancer especially the diffuse type. The first was a polymorphism (rs2294008) in prostate stem cell antigen (PSCA), and the other was a polymorphism (rs4072037) in mucin 1 (MUC1). DNA methylation is associated with gastric cancer and Helicobacter pylori (H. pylori)-induced gastritis, while hypermethylation of promoter CpG island (CGI) is a common characteristic of enlarged-fold gastritis induced by H. pylori, a risk factor of diffuse-type gastric cancer. We evaluated the association between PSCA and MUC1 polymorphisms with H. pylori-related promoter CGI methylation in the non-neoplastic gastric mucosa. PSCA rs2294008 C/T and MUC1 rs4072037 A/G polymorphisms were genotyped in 410 cancer-free subjects in relation to promoter CGI methylation status of three candidate genes, of which the methylation status is associated with H. pylori infection (IGF2, MYOD1, and SLC16A12). Methylation levels of all three genes were significantly higher in subjects with PSCA rs2294008 T/T compared with the PSCA rs2294008 C/C (all P < 0.05). Such associations were more enhanced in H. pylori–positive subjects (all P < 0.01). The multivariate analysis demonstrated that PSCA C/T [OR, 2.37; 95% CI (confidence interval), 1.06–5.29; P ¼ 0.035] and T/T genotypes (OR, 3.2; 95% CI, 1.41–7.25; P ¼ 0.005) were significantly associated with methylation-high gastric mucosa as independent factors. MUC1 rs4072037 A/G polymorphism was not associated with methylation status of all three genes. PSCA C/T and T/T genotypes are associated with H. pylori–related promoter DNA methylation in the gastric mucosa. Impact: Our observations provided the evidence that PSCA polymorphism influence the susceptibility to gastric cancer through DNA methylation induction.

Original languageEnglish
Pages (from-to)579-584
Number of pages6
JournalCancer Prevention Research
Volume12
Issue number9
DOIs
Publication statusPublished - 01-01-2019

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DNA Methylation
Prostate
Stomach
Stem Cells
Epithelium
Methylation
Antigens
Mucin-1
Helicobacter pylori
CpG Islands
Genes
Stomach Neoplasms
Viral Tumor Antigens
Gastric Mucosa
Gastritis
Genotype
Confidence Intervals
Genome-Wide Association Study
Helicobacter Infections
Single Nucleotide Polymorphism

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Tahara, Tomomitsu ; Tahara, Sayumi ; Horiguchi, Noriyuki ; Kato, Takema ; Shinkai, Yasuko ; Okubo, Masaaki ; Terada, Tsuyoshi ; Yoshida, Dai ; Funasaka, Kohei ; Nagasaka, Mitsuo ; Nakagawa, Yoshihito ; Kurahashi, Hiroki ; Shibata, Tomoyuki ; Tsukamoto, Tetsuya ; Omiya, Naoki. / Prostate stem cell antigen gene polymorphism is associated with H. Pylori–related promoter DNA methylation in nonneoplastic gastric epithelium. In: Cancer Prevention Research. 2019 ; Vol. 12, No. 9. pp. 579-584.
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title = "Prostate stem cell antigen gene polymorphism is associated with H. Pylori–related promoter DNA methylation in nonneoplastic gastric epithelium",
abstract = "Genome-wide association study identified two functional SNPs associated with gastric cancer especially the diffuse type. The first was a polymorphism (rs2294008) in prostate stem cell antigen (PSCA), and the other was a polymorphism (rs4072037) in mucin 1 (MUC1). DNA methylation is associated with gastric cancer and Helicobacter pylori (H. pylori)-induced gastritis, while hypermethylation of promoter CpG island (CGI) is a common characteristic of enlarged-fold gastritis induced by H. pylori, a risk factor of diffuse-type gastric cancer. We evaluated the association between PSCA and MUC1 polymorphisms with H. pylori-related promoter CGI methylation in the non-neoplastic gastric mucosa. PSCA rs2294008 C/T and MUC1 rs4072037 A/G polymorphisms were genotyped in 410 cancer-free subjects in relation to promoter CGI methylation status of three candidate genes, of which the methylation status is associated with H. pylori infection (IGF2, MYOD1, and SLC16A12). Methylation levels of all three genes were significantly higher in subjects with PSCA rs2294008 T/T compared with the PSCA rs2294008 C/C (all P < 0.05). Such associations were more enhanced in H. pylori–positive subjects (all P < 0.01). The multivariate analysis demonstrated that PSCA C/T [OR, 2.37; 95{\%} CI (confidence interval), 1.06–5.29; P ¼ 0.035] and T/T genotypes (OR, 3.2; 95{\%} CI, 1.41–7.25; P ¼ 0.005) were significantly associated with methylation-high gastric mucosa as independent factors. MUC1 rs4072037 A/G polymorphism was not associated with methylation status of all three genes. PSCA C/T and T/T genotypes are associated with H. pylori–related promoter DNA methylation in the gastric mucosa. Impact: Our observations provided the evidence that PSCA polymorphism influence the susceptibility to gastric cancer through DNA methylation induction.",
author = "Tomomitsu Tahara and Sayumi Tahara and Noriyuki Horiguchi and Takema Kato and Yasuko Shinkai and Masaaki Okubo and Tsuyoshi Terada and Dai Yoshida and Kohei Funasaka and Mitsuo Nagasaka and Yoshihito Nakagawa and Hiroki Kurahashi and Tomoyuki Shibata and Tetsuya Tsukamoto and Naoki Omiya",
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Prostate stem cell antigen gene polymorphism is associated with H. Pylori–related promoter DNA methylation in nonneoplastic gastric epithelium. / Tahara, Tomomitsu; Tahara, Sayumi; Horiguchi, Noriyuki; Kato, Takema; Shinkai, Yasuko; Okubo, Masaaki; Terada, Tsuyoshi; Yoshida, Dai; Funasaka, Kohei; Nagasaka, Mitsuo; Nakagawa, Yoshihito; Kurahashi, Hiroki; Shibata, Tomoyuki; Tsukamoto, Tetsuya; Omiya, Naoki.

In: Cancer Prevention Research, Vol. 12, No. 9, 01.01.2019, p. 579-584.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Prostate stem cell antigen gene polymorphism is associated with H. Pylori–related promoter DNA methylation in nonneoplastic gastric epithelium

AU - Tahara, Tomomitsu

AU - Tahara, Sayumi

AU - Horiguchi, Noriyuki

AU - Kato, Takema

AU - Shinkai, Yasuko

AU - Okubo, Masaaki

AU - Terada, Tsuyoshi

AU - Yoshida, Dai

AU - Funasaka, Kohei

AU - Nagasaka, Mitsuo

AU - Nakagawa, Yoshihito

AU - Kurahashi, Hiroki

AU - Shibata, Tomoyuki

AU - Tsukamoto, Tetsuya

AU - Omiya, Naoki

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Genome-wide association study identified two functional SNPs associated with gastric cancer especially the diffuse type. The first was a polymorphism (rs2294008) in prostate stem cell antigen (PSCA), and the other was a polymorphism (rs4072037) in mucin 1 (MUC1). DNA methylation is associated with gastric cancer and Helicobacter pylori (H. pylori)-induced gastritis, while hypermethylation of promoter CpG island (CGI) is a common characteristic of enlarged-fold gastritis induced by H. pylori, a risk factor of diffuse-type gastric cancer. We evaluated the association between PSCA and MUC1 polymorphisms with H. pylori-related promoter CGI methylation in the non-neoplastic gastric mucosa. PSCA rs2294008 C/T and MUC1 rs4072037 A/G polymorphisms were genotyped in 410 cancer-free subjects in relation to promoter CGI methylation status of three candidate genes, of which the methylation status is associated with H. pylori infection (IGF2, MYOD1, and SLC16A12). Methylation levels of all three genes were significantly higher in subjects with PSCA rs2294008 T/T compared with the PSCA rs2294008 C/C (all P < 0.05). Such associations were more enhanced in H. pylori–positive subjects (all P < 0.01). The multivariate analysis demonstrated that PSCA C/T [OR, 2.37; 95% CI (confidence interval), 1.06–5.29; P ¼ 0.035] and T/T genotypes (OR, 3.2; 95% CI, 1.41–7.25; P ¼ 0.005) were significantly associated with methylation-high gastric mucosa as independent factors. MUC1 rs4072037 A/G polymorphism was not associated with methylation status of all three genes. PSCA C/T and T/T genotypes are associated with H. pylori–related promoter DNA methylation in the gastric mucosa. Impact: Our observations provided the evidence that PSCA polymorphism influence the susceptibility to gastric cancer through DNA methylation induction.

AB - Genome-wide association study identified two functional SNPs associated with gastric cancer especially the diffuse type. The first was a polymorphism (rs2294008) in prostate stem cell antigen (PSCA), and the other was a polymorphism (rs4072037) in mucin 1 (MUC1). DNA methylation is associated with gastric cancer and Helicobacter pylori (H. pylori)-induced gastritis, while hypermethylation of promoter CpG island (CGI) is a common characteristic of enlarged-fold gastritis induced by H. pylori, a risk factor of diffuse-type gastric cancer. We evaluated the association between PSCA and MUC1 polymorphisms with H. pylori-related promoter CGI methylation in the non-neoplastic gastric mucosa. PSCA rs2294008 C/T and MUC1 rs4072037 A/G polymorphisms were genotyped in 410 cancer-free subjects in relation to promoter CGI methylation status of three candidate genes, of which the methylation status is associated with H. pylori infection (IGF2, MYOD1, and SLC16A12). Methylation levels of all three genes were significantly higher in subjects with PSCA rs2294008 T/T compared with the PSCA rs2294008 C/C (all P < 0.05). Such associations were more enhanced in H. pylori–positive subjects (all P < 0.01). The multivariate analysis demonstrated that PSCA C/T [OR, 2.37; 95% CI (confidence interval), 1.06–5.29; P ¼ 0.035] and T/T genotypes (OR, 3.2; 95% CI, 1.41–7.25; P ¼ 0.005) were significantly associated with methylation-high gastric mucosa as independent factors. MUC1 rs4072037 A/G polymorphism was not associated with methylation status of all three genes. PSCA C/T and T/T genotypes are associated with H. pylori–related promoter DNA methylation in the gastric mucosa. Impact: Our observations provided the evidence that PSCA polymorphism influence the susceptibility to gastric cancer through DNA methylation induction.

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