title: Relationship of the methylenetetrahydrofolate reductase C677T polymorphism with microsatellite instability and promoter hypermethylation in sporadic colorectal cancer.
abstract: The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is associated with the expression of a thermolabile enzyme with decreased activity that influences the pool of methyl-donor molecules. Several studies have reported an association between C677T polymorphism and susceptibility to colorectal cancer (CRC). Considering that methylation abnormalities appear to be important for the pathogenesis of CRC, we examined the correlation between the genotype of the MTHFR C677T polymorphism, hypermethylation of the promoter region of five relevant genes (DAPK, MGMT, hMLH1, p16(INK4a), and p14(ARF)), and microsatellite instability, in 106 patients with primary CRCs in Brazil. We did not find significant differences in the genotypic frequencies of the MTHFR C677T polymorphism when one or more loci were hypermethylated. However, we did find a significant excess of 677TT individuals among patients with CRC who had microsatellite instability. This strong association was independent of the methylation status of hMLH1 and of the biogeographical genomic ancestry of the patients. Although the mechanism responsible for the link between the C677T polymorphism and microsatellite instability was not apparent, this finding may provide a clue towards a better understanding of the pathogenesis of microsatellite instability in human colorectal cancer.
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil.
authors.forename: Alessandra D
authors.initials: AD
authors.lastname: Clarizia
authors.forename: Luciana
authors.initials: L
authors.lastname: Bastos-Rodrigues
authors.forename: Heloísa B
authors.initials: HB
authors.lastname: Pena
authors.forename: Charles
authors.initials: C
authors.lastname: Anacleto
authors.forename: Benedito
authors.initials: B
authors.lastname: Rossi
authors.forename: Fernando A
authors.initials: FA
authors.lastname: Soares
authors.forename: Ademar
authors.initials: A
authors.lastname: Lopes
authors.forename: José Cláudio C
authors.initials: JC
authors.lastname: Rocha
authors.forename: Otávia
authors.initials: O
authors.lastname: Caballero
authors.forename: Anamaria
authors.initials: A
authors.lastname: Camargo
authors.forename: Andrew J G
authors.initials: AJ
authors.lastname: Simpson
authors.forename: Sérgio D J
authors.initials: SD
authors.lastname: Pena
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D020022:Genetic Predisposition to Disease; D042822:Genomic Instability / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D042965:Methylenetetrahydrofolate Reductase (NADPH2)