Relationship of the methylenetetrahydrofolate reductase C677T polymorphism with microsatellite instability and promoter hypermethylation in sporadic colorectal cancer
Genet. mol. res. (Online)
;
5(2): 315-322, 2006. tab
Artigo
em Inglês
| LILACS
| ID: lil-442567
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.
Texto completo:
DisponíveL
Índice:
LILACS (Américas)
Assunto principal:
Polimorfismo Genético
/
Neoplasias Colorretais
/
Biomarcadores Tumorais
/
Metilação de DNA
Tipo de estudo:
Estudo observacional
/
Fatores de risco
Limite:
Feminino
/
Humanos
/
Masculino
Idioma:
Inglês
Revista:
Genet. mol. res. (Online)
Assunto da revista:
Biologia Molecular
/
Genética
Ano de publicação:
2006
Tipo de documento:
Artigo
País de afiliação:
Brasil
Instituição/País de afiliação:
Hospital A. C. Camargo/BR
/
Ludwig Institute for Cancer Research/US
/
Universidade Federal de Minas Gerais/BR
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