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Research Article

Prostate stem cell antigen gene polymorphism is associated with H. pylori-related promoter DNA methylation in non-neoplastic 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 and Naoki Ohmiya
Tomomitsu Tahara
Gastroenterology, Fujita Health University
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  • For correspondence: tomomiccyu@yahoo.co.jp
Sayumi Tahara
Fujita Health University
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Noriyuki Horiguchi
Fujita Health University
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Takema Kato
Fujita Health University
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Yasuko Shinkai
Division of Molecular Genetics, Fujita Health University
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Masaaki Okubo
Fujita Health University
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Tsuyoshi Terada
Fujita Health University
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Dai Yoshida
Gastroenterology, Fujita Health University
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Kohei Funasaka
Gastroenterology, Fujita Health University
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Mitsuo Nagasaka
Fujita Health University
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Yoshihito Nakagawa
Gastroenterology, Fujita Health University
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Hiroki Kurahashi
Division of Molecular Genetics, ICMS, Fujita Health Universiry
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Tomoyuki Shibata
Gastroenterology, Fujita Health University
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Tetsuya Tsukamoto
Department of Diagnostic Pathology, ujita Health University School of Medicine
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Naoki Ohmiya
Department of Gastroenterology, Nagoya University Graduate School of Medicine
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DOI: 10.1158/1940-6207.CAPR-19-0035
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Abstract

Genome-wide association study identified two functional single nucleotide polymorphisms associated with gastric cancer (GC) 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 GC and 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 GC. 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 to 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 (odds ratio: 2.37, confidence interval: 1.06-5.29, P=0.035) and T/T genotypes (odds ratio: 3.2, confidence interval: 1.41-7.25, P=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.

  • Received January 16, 2019.
  • Revision received April 25, 2019.
  • Accepted June 14, 2019.
  • Copyright ©2019, American Association for Cancer Research.

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Published OnlineFirst June 18, 2019
doi: 10.1158/1940-6207.CAPR-19-0035

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Prostate stem cell antigen gene polymorphism is associated with H. pylori-related promoter DNA methylation in non-neoplastic 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 and Naoki Ohmiya
Cancer Prev Res June 18 2019 DOI: 10.1158/1940-6207.CAPR-19-0035

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Prostate stem cell antigen gene polymorphism is associated with H. pylori-related promoter DNA methylation in non-neoplastic 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 and Naoki Ohmiya
Cancer Prev Res June 18 2019 DOI: 10.1158/1940-6207.CAPR-19-0035
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eISSN: 1940-6215
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