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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.

C. Guerreiro,B. Carmona,S. Gonçalves,E. Carolino,P. Fidalgo,M. Brito,C. N. Leitão,M. Cravo

Published 2008 in American Journal of Clinical Nutrition

ABSTRACT

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 with CRC (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 microg/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 C677T MTHFR variant (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 of CRC 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.

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