Unesp Ciência, 2010, ano 1, número 5

Revista elaborada pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Risk of colorectal cancer associated with the C677T polymorphism in 5,10-methylenetetrahydrofolate reductase in Portuguese patients depends on the intake of methyl-donor nutrients

Background: Polymorphisms located in genes involved in the metabolism of folate and some methyl-related nutrients are implicated in colorectal cancer (CRC). Objective: We evaluated the association of 3 genetic polymorphisms [C677T MTHFR (methylene tetrahydrofolate reductase), A2756G MTR (methionine synthase), and C1420T SHMT (serine hydroxymethyltransferase)] with the intake of methyl-donor nutrients in CRC risk. Design: Patients withCRC(n 196) and healthy controls (n 200) matched for age and sex were evaluated for intake of methyl-donor nutrients and the 3 polymorphisms. Results: Except for folate intake, which was significantly lower in patients (P 0.02), no differences were observed in the dietary intake of other methyl-donor nutrients between groups. High intake of folate ( 406.7 g/d) was associated with a significantly lower risk of CRC (odds ratio: 0.67; 95% CI: 0.45, 0.99). The A2756G MTR polymorphism was not associated with the risk of developing CRC. In contrast, homozygosity for the C677TMTHFRvariant (TT) presented a 3.0-fold increased risk of CRC (95% CI: 1.3, 6.7). Similarly, homozygosity for the C1420T SHMT polymorphism also had a 2.6-fold increased risk (95% CI: 1.1, 5.9) of developing CRC. When interactions between variables were studied, low intake of all methyl-donor nutrients was associated with an increased risk ofCRC in homozygous participants for the C677T MTHFR polymorphism, but a statistically significant interaction was only observed for folate (odds ratio: 14.0; 95% CI: 1.8, 108.5). No significant associations were seen for MTR or SHMT polymorphisms. Conclusion: These results show an association between the C677T MTHFR variant and different folate intakes on risk of CRC.

Unesp Ciência, 2013, ano 5, número 45

Revista elaborada pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Unesp Ciência, 2013, ano 5, número 46

Revista elaborada pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Unesp Ciência, 2013, ano 5, número 47

Revista elaborada pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Unesp Ciência, 2013, ano 5, número 48

Revista elaborada pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Unesp Ciência, 2014, ano 5, número 49

Revista elaborada pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Unesp Ciência, 2014, ano 5, número 50

Revista elaborada pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Unesp Ciência, 2014, ano 5, número 51

Revista elaborada pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Unesp Ciência, 2014, ano 5, número 52

Revista elaborada pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Unesp Ciência, 2014, ano 5, número 53

Revista elaborada pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Unesp Ciência, 2014, ano 5, número 54

Revista elaborada pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Unesp Ciência, 2014, ano 5, número 55

Revista elaborada pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

5' and 3' UTR thymidylate synthase polymorphisms modulate the risk of colorectal cancer independently of the intake of methyl group donors

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.