Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.21/3073
Título: 5' and 3' UTR thymidylate synthase polymorphisms modulate the risk of colorectal cancer independently of the intake of methyl group donors
Autor: Carmona, Bruno
Guerreiro, Catarina Sousa
Cravo, Marília
Leitão, Carlos Nobre
Brito, Miguel
Palavras-chave: Colorectal cancer
DNA synthesis
Data: Set-2008
Editora: Spandidos Publications
Citação: Carmona B, Guerreiro C, Cravo M, Nobre-Leitão C, Brito M. 5' and 3' UTR thymidylate synthase polymorphisms modulate the risk of colorectal cancer independently of the intake of methyl group donors. Mol Med Rep. 2008;1(5):747-52.
Resumo: Thymidylate synthase, as a rate-limiting step in DNA synthesis, catalyses the conversion of dUMP into dTMP using 5,10-methylenotetrahydrofolate as the methyl donor. Two polymorphisms have been described in this gene: a repeat polymorphism in the 5' promoter enhancer region (3R versus 2R) and a 6 bp deletion in the 3' unstranslated region. Both of these may affect protein levels. The present case control study was aimed at investigating the influence of these two polymorphisms on the development of colorectal cancer (CRC), as well as their potential interaction with folate, vitamin B6 and vitamin B12 intake. A total of 196 cases and 200 controls, matched for age and sex distribution, were included in the study. No association was found between CRC and the 28 bp repeat polymorphism, but it was observed that individuals with the 6 bp/del and del/del genotypes had a significantly lower risk of developing the disease (OR=0.47; 95% CI 0.30-0.72). A combined genotype (2R/2R; 6 bp/del+del/del) was also found, which was associated with an even lower risk of developing of the disease (OR=0.42; 95% CI 0.26-0.69). No significant interaction between these polymorphisms and vitamin intake was observed. These results indicate for the first time that the 6 bp/del allele might be a protective factor in the development of CRC, independent of the intake of methyl group donors.
Peer review: yes
URI: http://hdl.handle.net/10400.21/3073
ISSN: 1791-3004
Versão do Editor: http://www.spandidos-publications.com/mmr/1/5/747
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