We performed a case-control study to examine the relationship between @entity9769 @entity9770 gene polymorphism (MTHFR @entity9770 ) and @entity356 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 @entity9769 677T/T genotype and carriers of the wild-type MTHFR677C/C genotype. Lymphocyte genomic DNA from 162 @entity356 @entity1 and 164 controls was used for MTHFR @entity9770 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 @entity5498 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 @entity9769 677T/T genotype. The global allelic distribution was in Hardy-Weinberg equilibrium. The @entity9769 677T allele was significantly associated with @entity356 risk with an OR of 2.49 (95% CI 1.48-4.20) in heterozygous MTHFR @entity9770 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 @entity5 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, @entity9769 677T played the role of a moderate-penetrance @entity356 susceptibility allele. Possession of the @entity9769 677T/T genotype was significantly associated with genomic DNA hypomethylation. These findings deserve further investigation in the context of novel strategies for @entity356 prevention.

Methylenetetrahydrofolate reductase @entity9770 gene polymorphism, XXXX susceptibility and genomic DNA hypomethylation in an at-risk Italian population.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity9770 :: ('c|SUB|C|677|T', 'DNAMutation') :: ['677C/T', 'C677T'] @entity9769 :: ('4524', 'Gene') :: ['MTHFR'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity5498 :: ('CHEBI:32875', 'Chemical') :: ['methyl'] @entity356 :: ('MESH:D013274', 'Disease') :: ['gastric cancer']
@entity356 :: (MESH:D013274,Disease) :: ['gastric cancer']
