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

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

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Abstract

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 65yr 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 65yr 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.

Original languageEnglish
Pages (from-to)835-845
Number of pages11
JournalMolecular Carcinogenesis
Volume50
Issue number11
DOIs
Publication statusPublished - 01-11-2011

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CpG Islands
Gastric Mucosa
Interleukin-1
Methylation
Genes
Death-Associated Protein Kinases
Genotype
Carcinogenesis
Tumor Suppressor Protein p14ARF
p16 Genes
Helicobacter Infections
Cadherins
Helicobacter pylori

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cancer Research

Cite this

Tahara, Tomomitsu ; Shibata, Tomoyuki ; Nakamura, Masakatsu ; Yamashita, Hiromi ; Yoshioka, Daisuke ; Okubo, Masaaki ; Yonemura, Joh ; Kamiya, Yoshio ; Ishizuka, Takamitsu ; Hirata, Ichiro ; Arisawa, Tomiyasu. / Effect of polymorphisms of IL-1β and TNF-α genes on CpG island hyper methylation (CIHM) in the nonneoplastic gastric mucosa. In: Molecular Carcinogenesis. 2011 ; Vol. 50, No. 11. pp. 835-845.
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abstract = "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 65yr 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 65yr 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.",
author = "Tomomitsu Tahara and Tomoyuki Shibata and Masakatsu Nakamura and Hiromi Yamashita and Daisuke Yoshioka and Masaaki Okubo and Joh Yonemura and Yoshio Kamiya and Takamitsu Ishizuka and Ichiro Hirata and Tomiyasu Arisawa",
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Tahara, T, Shibata, T, Nakamura, M, Yamashita, H, Yoshioka, D, Okubo, M, Yonemura, J, Kamiya, Y, Ishizuka, T, Hirata, I & Arisawa, T 2011, 'Effect of polymorphisms of IL-1β and TNF-α genes on CpG island hyper methylation (CIHM) in the nonneoplastic gastric mucosa', Molecular Carcinogenesis, vol. 50, no. 11, pp. 835-845. https://doi.org/10.1002/mc.20759

Effect of polymorphisms of IL-1β and TNF-α genes on CpG island hyper methylation (CIHM) in the nonneoplastic gastric mucosa. / Tahara, Tomomitsu; Shibata, Tomoyuki; Nakamura, Masakatsu; Yamashita, Hiromi; Yoshioka, Daisuke; Okubo, Masaaki; Yonemura, Joh; Kamiya, Yoshio; Ishizuka, Takamitsu; Hirata, Ichiro; Arisawa, Tomiyasu.

In: Molecular Carcinogenesis, Vol. 50, No. 11, 01.11.2011, p. 835-845.

Research output: Contribution to journalArticle

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T1 - Effect of polymorphisms of IL-1β and TNF-α genes on CpG island hyper methylation (CIHM) in the nonneoplastic gastric mucosa

AU - Tahara, Tomomitsu

AU - Shibata, Tomoyuki

AU - Nakamura, Masakatsu

AU - Yamashita, Hiromi

AU - Yoshioka, Daisuke

AU - Okubo, Masaaki

AU - Yonemura, Joh

AU - Kamiya, Yoshio

AU - Ishizuka, Takamitsu

AU - Hirata, Ichiro

AU - Arisawa, Tomiyasu

PY - 2011/11/1

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N2 - 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 65yr 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 65yr 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.

AB - 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 65yr 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 65yr 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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