Polymorphisms of DNA Repair and Xenobiotic Genes Predispose to CpG Island Methylation in Non-Neoplastic Gastric Mucosa

Tomomitsu Tahara, Tomoyuki Shibata, Masakatsu Nakamura, Masaaki Okubo, Hiromi Yamashita, Daisuke Yoshioka, Joh Yonemura, Takamitsu Ishizuka, Ichiro Hirata, Tomiyasu Arisawa

Research output: Contribution to journalArticle

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Abstract

Background: Genetic factors, related to DNA repair or xenobiotic pathways might confer different degrees of susceptibility to gastric carcinogenesis. CpG island hyper methylation (CIHM) is a major event in gastric carcinogenesis. We evaluated the association between XRCC1, GSTP1, GSTT1 and GSTM1 polymorphisms with CIHM status in non-neoplastic gastric mucosa. Methods: XRCC1 Arg399Gln, and Arg194Trp, GSTP1 Ile104Val, and GSTT1, GSTM1 null polymorphisms were genotyped in 415 cancer free subjects, in relation to four candidate CpG (p14, p16, DAP-kinase and CDH1) loci, assessed by Methylation-Specific-Polymerase Chain Reaction (MSP). CIHM high was defined as two or more CpG islands methylated. Results: Significant association between XRCC1 codon 399 Gln/Gln genotype and reduced susceptibility to CIHM of DAP-kinase (adjusted OR=0.30, 95%CI=0.13-0.71, p=0055) and CIHM high (OR=0.42, 95%CI=0.19-0.97, p=04). XRCC1 codon 399 Gin/Gln genotype also presented lower number of CIHM when compared with both Arg/Gln, and Arg/Arg + Arg/Gln genotypes (p=02, .046, respectively) When subjects were divided according to age (>50 and <50), an association was found between GSTM1 null genotype and increased susceptibility to CIHM high in the 50years and older generations (OR=1.63, 95%CI=1.01-2.62, p=045). Conclusion: XRCC1 codon 399 Gln/Gln genotype is associated with reduced susceptibility to CIHM especially DAP-kinase. GSTM1 null genotype may increase the susceptibility to CIHM especially in older patients. Genetic factors, related to DNA repair or xenobiotic pathways may have a role in CIHM-related gastric carcinogenesis.

Original languageEnglish
Pages (from-to)99-106
Number of pages8
JournalHelicobacter
Volume16
Issue number2
DOIs
Publication statusPublished - 01-04-2011

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CpG Islands
Xenobiotics
Gastric Mucosa
DNA Repair
Methylation
Genes
Death-Associated Protein Kinases
Genotype
Codon
Stomach
Carcinogenesis

All Science Journal Classification (ASJC) codes

  • Gastroenterology
  • Infectious Diseases

Cite this

Tahara, Tomomitsu ; Shibata, Tomoyuki ; Nakamura, Masakatsu ; Okubo, Masaaki ; Yamashita, Hiromi ; Yoshioka, Daisuke ; Yonemura, Joh ; Ishizuka, Takamitsu ; Hirata, Ichiro ; Arisawa, Tomiyasu. / Polymorphisms of DNA Repair and Xenobiotic Genes Predispose to CpG Island Methylation in Non-Neoplastic Gastric Mucosa. In: Helicobacter. 2011 ; Vol. 16, No. 2. pp. 99-106.
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title = "Polymorphisms of DNA Repair and Xenobiotic Genes Predispose to CpG Island Methylation in Non-Neoplastic Gastric Mucosa",
abstract = "Background: Genetic factors, related to DNA repair or xenobiotic pathways might confer different degrees of susceptibility to gastric carcinogenesis. CpG island hyper methylation (CIHM) is a major event in gastric carcinogenesis. We evaluated the association between XRCC1, GSTP1, GSTT1 and GSTM1 polymorphisms with CIHM status in non-neoplastic gastric mucosa. Methods: XRCC1 Arg399Gln, and Arg194Trp, GSTP1 Ile104Val, and GSTT1, GSTM1 null polymorphisms were genotyped in 415 cancer free subjects, in relation to four candidate CpG (p14, p16, DAP-kinase and CDH1) loci, assessed by Methylation-Specific-Polymerase Chain Reaction (MSP). CIHM high was defined as two or more CpG islands methylated. Results: Significant association between XRCC1 codon 399 Gln/Gln genotype and reduced susceptibility to CIHM of DAP-kinase (adjusted OR=0.30, 95{\%}CI=0.13-0.71, p=0055) and CIHM high (OR=0.42, 95{\%}CI=0.19-0.97, p=04). XRCC1 codon 399 Gin/Gln genotype also presented lower number of CIHM when compared with both Arg/Gln, and Arg/Arg + Arg/Gln genotypes (p=02, .046, respectively) When subjects were divided according to age (>50 and <50), an association was found between GSTM1 null genotype and increased susceptibility to CIHM high in the 50years and older generations (OR=1.63, 95{\%}CI=1.01-2.62, p=045). Conclusion: XRCC1 codon 399 Gln/Gln genotype is associated with reduced susceptibility to CIHM especially DAP-kinase. GSTM1 null genotype may increase the susceptibility to CIHM especially in older patients. Genetic factors, related to DNA repair or xenobiotic pathways may have a role in CIHM-related gastric carcinogenesis.",
author = "Tomomitsu Tahara and Tomoyuki Shibata and Masakatsu Nakamura and Masaaki Okubo and Hiromi Yamashita and Daisuke Yoshioka and Joh Yonemura and Takamitsu Ishizuka and Ichiro Hirata and Tomiyasu Arisawa",
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Tahara, T, Shibata, T, Nakamura, M, Okubo, M, Yamashita, H, Yoshioka, D, Yonemura, J, Ishizuka, T, Hirata, I & Arisawa, T 2011, 'Polymorphisms of DNA Repair and Xenobiotic Genes Predispose to CpG Island Methylation in Non-Neoplastic Gastric Mucosa', Helicobacter, vol. 16, no. 2, pp. 99-106. https://doi.org/10.1111/j.1523-5378.2011.00821.x

Polymorphisms of DNA Repair and Xenobiotic Genes Predispose to CpG Island Methylation in Non-Neoplastic Gastric Mucosa. / Tahara, Tomomitsu; Shibata, Tomoyuki; Nakamura, Masakatsu; Okubo, Masaaki; Yamashita, Hiromi; Yoshioka, Daisuke; Yonemura, Joh; Ishizuka, Takamitsu; Hirata, Ichiro; Arisawa, Tomiyasu.

In: Helicobacter, Vol. 16, No. 2, 01.04.2011, p. 99-106.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Polymorphisms of DNA Repair and Xenobiotic Genes Predispose to CpG Island Methylation in Non-Neoplastic Gastric Mucosa

AU - Tahara, Tomomitsu

AU - Shibata, Tomoyuki

AU - Nakamura, Masakatsu

AU - Okubo, Masaaki

AU - Yamashita, Hiromi

AU - Yoshioka, Daisuke

AU - Yonemura, Joh

AU - Ishizuka, Takamitsu

AU - Hirata, Ichiro

AU - Arisawa, Tomiyasu

PY - 2011/4/1

Y1 - 2011/4/1

N2 - Background: Genetic factors, related to DNA repair or xenobiotic pathways might confer different degrees of susceptibility to gastric carcinogenesis. CpG island hyper methylation (CIHM) is a major event in gastric carcinogenesis. We evaluated the association between XRCC1, GSTP1, GSTT1 and GSTM1 polymorphisms with CIHM status in non-neoplastic gastric mucosa. Methods: XRCC1 Arg399Gln, and Arg194Trp, GSTP1 Ile104Val, and GSTT1, GSTM1 null polymorphisms were genotyped in 415 cancer free subjects, in relation to four candidate CpG (p14, p16, DAP-kinase and CDH1) loci, assessed by Methylation-Specific-Polymerase Chain Reaction (MSP). CIHM high was defined as two or more CpG islands methylated. Results: Significant association between XRCC1 codon 399 Gln/Gln genotype and reduced susceptibility to CIHM of DAP-kinase (adjusted OR=0.30, 95%CI=0.13-0.71, p=0055) and CIHM high (OR=0.42, 95%CI=0.19-0.97, p=04). XRCC1 codon 399 Gin/Gln genotype also presented lower number of CIHM when compared with both Arg/Gln, and Arg/Arg + Arg/Gln genotypes (p=02, .046, respectively) When subjects were divided according to age (>50 and <50), an association was found between GSTM1 null genotype and increased susceptibility to CIHM high in the 50years and older generations (OR=1.63, 95%CI=1.01-2.62, p=045). Conclusion: XRCC1 codon 399 Gln/Gln genotype is associated with reduced susceptibility to CIHM especially DAP-kinase. GSTM1 null genotype may increase the susceptibility to CIHM especially in older patients. Genetic factors, related to DNA repair or xenobiotic pathways may have a role in CIHM-related gastric carcinogenesis.

AB - Background: Genetic factors, related to DNA repair or xenobiotic pathways might confer different degrees of susceptibility to gastric carcinogenesis. CpG island hyper methylation (CIHM) is a major event in gastric carcinogenesis. We evaluated the association between XRCC1, GSTP1, GSTT1 and GSTM1 polymorphisms with CIHM status in non-neoplastic gastric mucosa. Methods: XRCC1 Arg399Gln, and Arg194Trp, GSTP1 Ile104Val, and GSTT1, GSTM1 null polymorphisms were genotyped in 415 cancer free subjects, in relation to four candidate CpG (p14, p16, DAP-kinase and CDH1) loci, assessed by Methylation-Specific-Polymerase Chain Reaction (MSP). CIHM high was defined as two or more CpG islands methylated. Results: Significant association between XRCC1 codon 399 Gln/Gln genotype and reduced susceptibility to CIHM of DAP-kinase (adjusted OR=0.30, 95%CI=0.13-0.71, p=0055) and CIHM high (OR=0.42, 95%CI=0.19-0.97, p=04). XRCC1 codon 399 Gin/Gln genotype also presented lower number of CIHM when compared with both Arg/Gln, and Arg/Arg + Arg/Gln genotypes (p=02, .046, respectively) When subjects were divided according to age (>50 and <50), an association was found between GSTM1 null genotype and increased susceptibility to CIHM high in the 50years and older generations (OR=1.63, 95%CI=1.01-2.62, p=045). Conclusion: XRCC1 codon 399 Gln/Gln genotype is associated with reduced susceptibility to CIHM especially DAP-kinase. GSTM1 null genotype may increase the susceptibility to CIHM especially in older patients. Genetic factors, related to DNA repair or xenobiotic pathways may have a role in CIHM-related gastric carcinogenesis.

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