PMID- 18097597
OWN - NLM
STAT- MEDLINE
DCOM- 20080212
LR  - 20081121
IS  - 1021-335X (Print)
IS  - 1021-335X (Linking)
VI  - 19
IP  - 1
DP  - 2008 Jan
TI  - The influence of promoter polymorphism of nuclear factor-erythroid 2-related 
      factor 2 gene on the aberrant DNA methylation in gastric epithelium.
PG  - 211-6
AB  - Aberrant promoter methylation is an important mechanism for gene silencing. 
      Inflammation-related reactive oxygens contribute to this CpG island methylation. 
      The nuclear factor-erythroid 2-related factor 2 gene (Nrf2) is known to regulate 
      the expression of detoxifying and antioxidant genes. We investigated the 
      relationship between promoter polymorphisms of Nrf2 gene and the CpG island 
      methylation in non-cancerous gastric mucosa. The study was performed in 85 
      subjects (46 without gastric malignancies, non-GC group, and 39 with gastric 
      cancer, GC group). The promoter methylation status of p14(ARF), p16(INK4a) and 
      p21(Waf1) genes was determined by methylation-specific-polymerase chain reaction. 
      The Nrf2 gene genotypes were determined by the PCR-SSCP method. In the 85 
      subjects, CpG island methylation was found in 25.9% for p14, 15.3% for p16, none 
      for p21. The frequency of the methylated genes was significantly higher in GC 
      group than non-GC group (OR, 2.67; 95% CI, 1.10-6.49; p=0.029). In particular, 
      the frequency of p16 gene methylation was much higher in GC group (p=0.0023). The 
      Nrf2 -686/-684 G/G haplotype was positively associated and A/G haplotype was 
      inversely associated with the development of CpG island methylation, especially 
      p14 gene methylation (OR, 3.28; 95% CI, 1.26-8.59; p=0.015, and OR, 0.38; 95% CI, 
      0.15-0.96; p=0.040, respectively). In Helicobacter pylori (H. pylori) infected 
      subjects, the number of -686/-684 G/G allele was positively correlated and that 
      of A/G allele was inversely correlated to the methylation status, especially p14 
      methylation, by the adjusted analysis (OR, 2.90; 95% CI, 1.14-7.36; p=0.026, and 
      OR, 0.33; 95% CI, 0.13-0.88; p=0.027, respectively). Our results suggested that 
      the promoter polymorphisms of Nrf2 gene may affect the methylation status of 
      tumor-related genes, especially the p14 gene, under the influence of H. 
      pylori-induced gastric inflammation.
FAU - Arisawa, Tomiyasu
AU  - Arisawa T
AD  - Department of Gatroenterology, Fujita Health University, School of Medicine, 
      Toyoake 470-1192, Japan. tarisawa@fujita-hu.ac.jp
FAU - Tahara, Tomomitsu
AU  - Tahara T
FAU - Shibata, Tomoyuki
AU  - Shibata T
FAU - Nagasaka, Mitsuo
AU  - Nagasaka M
FAU - Nakamura, Masakatsu
AU  - Nakamura M
FAU - Kamiya, Yoshio
AU  - Kamiya Y
FAU - Fujita, Hiroshi
AU  - Fujita H
FAU - Yoshioka, Daisuke
AU  - Yoshioka D
FAU - Arima, Yuko
AU  - Arima Y
FAU - Okubo, Masaaki
AU  - Okubo M
FAU - Hirata, Ichiro
AU  - Hirata I
FAU - Nakano, Hiroshi
AU  - Nakano H
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (NF-E2 Transcription Factor)
RN  - 0 (Tumor Suppressor Protein p14ARF)
SB  - IM
MH  - Aged
MH  - CpG Islands
MH  - *DNA Methylation
MH  - Female
MH  - Gastric Mucosa/*physiology
MH  - Gastritis/genetics/microbiology
MH  - Helicobacter Infections/complications
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - NF-E2 Transcription Factor/*genetics
MH  - Polymerase Chain Reaction
MH  - *Polymorphism, Single-Stranded Conformational
MH  - Promoter Regions, Genetic/genetics
MH  - Stomach Neoplasms/*genetics
MH  - Tumor Suppressor Protein p14ARF/genetics
EDAT- 2007/12/22 09:00
MHDA- 2008/02/13 09:00
CRDT- 2007/12/22 09:00
PHST- 2007/12/22 09:00 [pubmed]
PHST- 2008/02/13 09:00 [medline]
PHST- 2007/12/22 09:00 [entrez]
PST - ppublish
SO  - Oncol Rep. 2008 Jan;19(1):211-6.