MTHFR C677T polymorphism and differential methylation status in gastric cancer: an association with Helicobacter pylori infection

• Published in: Virchows Archiv : an international journal of pathology 2010-12, Vol.457 (6), p.627-633
• Main Authors: Neves Filho, Eduardo Henrique Cunha, Alves, Markenia Kelia Santos, Lima, Valeska Portela, Rabenhorst, Silvia Helena Barem
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adenocarcinoma - genetics; Adenocarcinoma - physiopathology; Adult; Aged; Aged, 80 and over; Alleles; Bacterial diseases; Bacterial diseases of the digestive system and abdomen; Biological and medical sciences; Cyclin-Dependent Kinase Inhibitor p16 - genetics; Cyclooxygenase 2 - genetics; Deoxyribonucleic acid; DNA; DNA Methylation - physiology; DNA, Neoplasm - physiology; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genotype; Helicobacter Infections - complications; Helicobacter Infections - physiopathology; Helicobacter pylori; Human bacterial diseases; Humans; Infectious diseases; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Medicine; Medicine & Public Health; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Middle Aged; MutL Protein Homolog 1; Nuclear Proteins - genetics; Original Article; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Polymorphism, Genetic - genetics; Retrospective Studies; Stomach Neoplasms - genetics; Stomach Neoplasms - physiopathology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors
• ISSN: 0945-6317; 1432-2307
• DOI: 10.1007/s00428-010-0996-3

MTHFR C677T and Helicobacter pylori infection are believed to play critical roles in the DNA methylation process, an epigenetic feature frequently found in gastric cancer. The aim of this study was to verify the associations between the MTHFR C677T polymorphism and the methylation status of three gastric cancer-related genes. The influence of H. pylori strains was also assessed. DNA extracted from 71 gastric tumor samples was available for MTHFR C677T genotyping by PCR-RFLP, promoter methylation identification by MS-PCR and H. pylori detection and posterior subtyping ( cag A and vac A genes) by PCR. In the distal tumors, a positive correlation was found between the methylation of CDKN2A and the allele T carriers ( r  = 0.357; p  = 0.009). Considering the eldest patients (age ≥ 60 years old), this correlation was even higher ( r  = 0,417; p  = 0.014). H. pylori infection by highly pathogenic strains ( cag A+/ vac As1m1) was also found correlated to promoter methylation of CDKN2A and the allele T carriers in distal tumors ( r  = 0.484; p  = 0.026). No significant correlation was verified between MTHFR C677T genotype and promoter methylation status when we analyzed the general sample. DNA methylation in CDKN2A associated to the MTHFR 677T carrier is suggested to be a distal tumor characteristic, especially in those 60 years old or older, and it seems to depend on the infection by H. pylori cag A/ vac As1m1 strains.