Risk of colorectal cancer associated with the C677T polymorphism in 5,10-methyl...

• Author(s): Guerreiro, Catarina Sousa ; Carmona, Bruno ; Gonçalves, Susana ; Carolino, Elisabete ; Fidalgo, Paulo ; Brito, Miguel ; Leitão, Carlos Nobre ; Cravo, Marília
• Date: 2008
• Persistent ID: http://hdl.handle.net/10400.21/3053
• Origin: Repositório Científico do Instituto Politécnico de Lisboa
• Subject(s): 5-Methyltetrahydrofolate-homocysteine S-methyltransferase; Case-control studies; Colorectal neoplasms/; Dose-response relationship, Drug; Folic acid; Glycine hydroxymethyltransferase; Methylenetetrahydrofolate reductase; Odds ratio; Polymorphism; Risk factor
• Document Type: Article
• Language: English

Description

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.