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

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

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

We performed a case-control study to examine the relationship between MTHFR C677T gene polymorphism (MTHFR677C/T) 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 MTHFR677T/T genotype and carriers of the wild-type MTHFR677C/C genotype. Lymphocyte genomic DNA from 162 gastric cancer patients and 164 controls was used for MTHFR677C/T 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 MTHFR677C/C genotype and 40 carriers of the MTHFR677T/T genotype. The global allelic distribution was in Hardy-Weinberg equilibrium. The MTHFR677T allele was significantly associated with gastric cancer risk with an OR of 2.49 (95% CI 1.48-4.20) in heterozygous MTHFR677C/T carriers and an OR of 2.85 (95% CI 1.52-5.35) in homozygous MTHFR677T/T carriers. This risk association was retained in subgroup analyses by tumor histotype and location. Genomic DNA hypomethylation status in MTHFR677T/T carriers was significantly higher than in subjects with wild-type MTHF677C/C genotype (p = 0.012). In the studied population, MTHFR677T played the role of a moderate-penetrance gastric cancer susceptibility allele. Possession of the MTHFR677T/T genotype was significantly associated with genomic DNA hypomethylation. These findings deserve further investigation in the context of novel strategies for gastric cancer prevention.

Original languageEnglish
Pages (from-to)628-632
Number of pages5
JournalInternational Journal of Cancer
Volume118
Issue number3
DOIs
Publication statusPublished - Mar 1 2006

Fingerprint

Methylenetetrahydrofolate Reductase (NADPH2)
Stomach Neoplasms
Genotype
DNA
Genes
Alleles
Penetrance
Enzyme Assays
DNA Methylation
Methylation
Italy
Case-Control Studies
Regression Analysis
Lymphocytes
Population
Neoplasms

Keywords

  • Cancer susceptibility
  • Gastric neoplasm
  • Methylation
  • Methylenetetrahydrofolate reductase
  • Polymorphism

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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

In: International Journal of Cancer, Vol. 118, No. 3, 01.03.2006, p. 628-632.

Research output: Contribution to journalArticle

Graziano, F, Kawakami, K, Ruzzo, A, Watanabe, G, Santini, D, Pizzagalli, F, Bisonni, R, Mari, D, Floriani, I, Catalano, V, Silva, R, Tonini, G, Torri, V, Giustini, L & Magnani, M 2006, 'Methylenetetrahydrofolate reductase 677C/T gene polymorphism, gastric cancer susceptibility and genomic DNA hypomethylation in an at-risk italian population', International Journal of Cancer, vol. 118, no. 3, pp. 628-632. https://doi.org/10.1002/ijc.21397
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. In: International Journal of Cancer. 2006 ; Vol. 118, No. 3. pp. 628-632.
@article{c6abbda0f036463d864e914a5d8d3474,
title = "Methylenetetrahydrofolate reductase 677C/T gene polymorphism, gastric cancer susceptibility and genomic DNA hypomethylation in an at-risk italian population",
abstract = "We performed a case-control study to examine the relationship between MTHFR C677T gene polymorphism (MTHFR677C/T) 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 MTHFR677T/T genotype and carriers of the wild-type MTHFR677C/C genotype. Lymphocyte genomic DNA from 162 gastric cancer patients and 164 controls was used for MTHFR677C/T 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 MTHFR677C/C genotype and 40 carriers of the MTHFR677T/T genotype. The global allelic distribution was in Hardy-Weinberg equilibrium. The MTHFR677T allele was significantly associated with gastric cancer risk with an OR of 2.49 (95{\%} CI 1.48-4.20) in heterozygous MTHFR677C/T carriers and an OR of 2.85 (95{\%} CI 1.52-5.35) in homozygous MTHFR677T/T carriers. This risk association was retained in subgroup analyses by tumor histotype and location. Genomic DNA hypomethylation status in MTHFR677T/T carriers was significantly higher than in subjects with wild-type MTHF677C/C genotype (p = 0.012). In the studied population, MTHFR677T played the role of a moderate-penetrance gastric cancer susceptibility allele. Possession of the MTHFR677T/T genotype was significantly associated with genomic DNA hypomethylation. These findings deserve further investigation in the context of novel strategies for gastric cancer prevention.",
keywords = "Cancer susceptibility, Gastric neoplasm, Methylation, Methylenetetrahydrofolate reductase, Polymorphism",
author = "Francesco Graziano and Kazuyuki Kawakami and Annamaria Ruzzo and Go Watanabe and Daniele Santini and Francesca Pizzagalli and Renato Bisonni and Davide Mari and Irene Floriani and Vincenzo Catalano and Rosarita Silva and Giuseppe Tonini and Valter Torri and Lucio Giustini and Mauro Magnani",
year = "2006",
month = "3",
day = "1",
doi = "10.1002/ijc.21397",
language = "English",
volume = "118",
pages = "628--632",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Methylenetetrahydrofolate reductase 677C/T gene polymorphism, gastric cancer susceptibility and genomic DNA hypomethylation in an at-risk italian population

AU - Graziano, Francesco

AU - Kawakami, Kazuyuki

AU - Ruzzo, Annamaria

AU - Watanabe, Go

AU - Santini, Daniele

AU - Pizzagalli, Francesca

AU - Bisonni, Renato

AU - Mari, Davide

AU - Floriani, Irene

AU - Catalano, Vincenzo

AU - Silva, Rosarita

AU - Tonini, Giuseppe

AU - Torri, Valter

AU - Giustini, Lucio

AU - Magnani, Mauro

PY - 2006/3/1

Y1 - 2006/3/1

N2 - We performed a case-control study to examine the relationship between MTHFR C677T gene polymorphism (MTHFR677C/T) 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 MTHFR677T/T genotype and carriers of the wild-type MTHFR677C/C genotype. Lymphocyte genomic DNA from 162 gastric cancer patients and 164 controls was used for MTHFR677C/T 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 MTHFR677C/C genotype and 40 carriers of the MTHFR677T/T genotype. The global allelic distribution was in Hardy-Weinberg equilibrium. The MTHFR677T allele was significantly associated with gastric cancer risk with an OR of 2.49 (95% CI 1.48-4.20) in heterozygous MTHFR677C/T carriers and an OR of 2.85 (95% CI 1.52-5.35) in homozygous MTHFR677T/T carriers. This risk association was retained in subgroup analyses by tumor histotype and location. Genomic DNA hypomethylation status in MTHFR677T/T carriers was significantly higher than in subjects with wild-type MTHF677C/C genotype (p = 0.012). In the studied population, MTHFR677T played the role of a moderate-penetrance gastric cancer susceptibility allele. Possession of the MTHFR677T/T genotype was significantly associated with genomic DNA hypomethylation. These findings deserve further investigation in the context of novel strategies for gastric cancer prevention.

AB - We performed a case-control study to examine the relationship between MTHFR C677T gene polymorphism (MTHFR677C/T) 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 MTHFR677T/T genotype and carriers of the wild-type MTHFR677C/C genotype. Lymphocyte genomic DNA from 162 gastric cancer patients and 164 controls was used for MTHFR677C/T 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 MTHFR677C/C genotype and 40 carriers of the MTHFR677T/T genotype. The global allelic distribution was in Hardy-Weinberg equilibrium. The MTHFR677T allele was significantly associated with gastric cancer risk with an OR of 2.49 (95% CI 1.48-4.20) in heterozygous MTHFR677C/T carriers and an OR of 2.85 (95% CI 1.52-5.35) in homozygous MTHFR677T/T carriers. This risk association was retained in subgroup analyses by tumor histotype and location. Genomic DNA hypomethylation status in MTHFR677T/T carriers was significantly higher than in subjects with wild-type MTHF677C/C genotype (p = 0.012). In the studied population, MTHFR677T played the role of a moderate-penetrance gastric cancer susceptibility allele. Possession of the MTHFR677T/T genotype was significantly associated with genomic DNA hypomethylation. These findings deserve further investigation in the context of novel strategies for gastric cancer prevention.

KW - Cancer susceptibility

KW - Gastric neoplasm

KW - Methylation

KW - Methylenetetrahydrofolate reductase

KW - Polymorphism

UR - http://www.scopus.com/inward/record.url?scp=30444442971&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=30444442971&partnerID=8YFLogxK

U2 - 10.1002/ijc.21397

DO - 10.1002/ijc.21397

M3 - Article

C2 - 16094648

AN - SCOPUS:30444442971

VL - 118

SP - 628

EP - 632

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 3

ER -