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Graziano, Francesco; Kawakami, Kazuyuki; Ruzzo, Annamaria; Watanabe, Go; Santini, Daniele; Pizzagalli, Francesca; Bisonni, Renato; Mari, Davide; Floriani, Irene; Catalano, Vincenzo; Silva, Rosarita; Tonini, Giuseppe; Torri, Valter; Giustini, Lucio; Magnani, Mauro

Methylenetetrahydrofolate reductase 677C/T gene polymorphism, gastric cancer susceptibility and genomic DNA hypomethylation in an at‐risk Italian population

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  • Medientyp: E-Artikel
  • Titel: Methylenetetrahydrofolate reductase 677C/T gene polymorphism, gastric cancer susceptibility and genomic DNA hypomethylation in an at‐risk Italian population
  • Beteiligte: Graziano, Francesco; Kawakami, Kazuyuki; Ruzzo, Annamaria; Watanabe, Go; Santini, Daniele; Pizzagalli, Francesca; Bisonni, Renato; Mari, Davide; Floriani, Irene; Catalano, Vincenzo; Silva, Rosarita; Tonini, Giuseppe; Torri, Valter; Giustini, Lucio; Magnani, Mauro
  • Erschienen: Wiley, 2006
  • Erschienen in: International Journal of Cancer
  • Sprache: Englisch
  • DOI: 10.1002/ijc.21397
  • ISSN: 1097-0215; 0020-7136
  • Schlagwörter: Cancer Research ; Oncology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>We performed a case‐control study to examine the relationship between <jats:italic>MTHFR C677T</jats:italic> gene polymorphism (<jats:italic>MTHFR677C/T</jats:italic>) and gastric cancer susceptibility in at‐risk populations in central Italy. To explore genomic DNA hypomethylation as a potential etiologic mechanism, this phenomenon was evaluated in carriers of the <jats:italic>MTHFR677T/T</jats:italic> genotype and carriers of the wild‐type <jats:italic>MTHFR677C/C</jats:italic> genotype. Lymphocyte genomic DNA from 162 gastric cancer patients and 164 controls was used for <jats:italic>MTHFR677C/T</jats:italic> genotyping. Unconditional regression analysis with ORs and 95% CIs was used to investigate the association of the polymorphism with disease. Genomic DNA methylation status by an established enzymatic assay that measures the DNA accepting capacity of methyl groups (inversely related to endogenous methylation) was assessed in a random sample of 40 carriers of the wild‐type <jats:italic>MTHFR677C/C</jats:italic> genotype and 40 carriers of the <jats:italic>MTHFR677T/T</jats:italic> genotype. The global allelic distribution was in Hardy‐Weinberg equilibrium. The <jats:italic>MTHFR677T</jats:italic> allele was significantly associated with gastric cancer risk with an OR of 2.49 (95% CI 1.48–4.20) in heterozygous <jats:italic>MTHFR677C/T</jats:italic> carriers and an OR of 2.85 (95% CI 1.52–5.35) in homozygous <jats:italic>MTHFR677T/T</jats:italic> carriers. This risk association was retained in subgroup analyses by tumor histotype and location. Genomic DNA hypomethylation status in <jats:italic>MTHFR677T/T</jats:italic> carriers was significantly higher than in subjects with wild‐type <jats:italic>MTHF677C/C</jats:italic> genotype (<jats:italic>p</jats:italic> = 0.012). In the studied population, <jats:italic>MTHFR677T</jats:italic> played the role of a moderate‐penetrance gastric cancer susceptibility allele. Possession of the <jats:italic>MTHFR677T/T</jats:italic> genotype was significantly associated with genomic DNA hypomethylation. These findings deserve further investigation in the context of novel strategies for gastric cancer prevention. © 2005 Wiley‐Liss, Inc.</jats:p>
  • Zugangsstatus: Freier Zugang