Alessandra D. Clarizia, Luciana Bastos-Rodrigues, Heloísa B. Pena, Charles Anacleto, Benedito Rossi, Fernando A. Soares,Ademar Lopes, José Cláudio C. Rocha, Otávia Caballero, Anamaria Camargo, Andrew J.G. Simpson4 and Sérgio D.J. Pena
Published May 17, 2006
Genet. Mol. Res. 5 (2): 315-322 (2006)
About the authors
Alessandra D. Clarizia, Luciana Bastos-Rodrigues, Heloísa B. Pena, Charles Anacleto, Benedito Rossi, Fernando A. Soares,Ademar Lopes, José Cláudio C. Rocha, Otávia Caballero, Anamaria Camargo, Andrew J.G. Simpson4 and Sérgio D.J. Pena
Corresponding author
S.D.J. Pena
E-mail: spena@dcc.ufmg.br
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, p16INK4a, and p14ARF), 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 patho genesis of microsatellite instability in human colorectal cancer.
Key words: Methylenetetrahydrofolate reductase, MTHFR, C677T polymorphism, Microsatellite instability, Hypermethylation, Colorectal cancer