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American Journal of Clinical Nutrition, Vol. 88, No. 5, 1413-1418, November 2008
© 2008 American Society for Nutrition

ORIGINAL RESEARCH COMMUNICATION

Risk of colorectal cancer associated with the C677T polymorphism in 5,10-methylenetetrahydrofolate reductase in Portuguese patients depends on the intake of methyl-donor nutrients1,2,3

Catarina Sousa Guerreiro, Bruno Carmona, Susana Gonçalves, Elisabete Carolino, Paulo Fidalgo, Miguel Brito, Carlos Nobre Leitão and Marília Cravo

1 From the Escola Superior de Tecnologia da Saúde de Lisboa, Unidade de Nutrição e Metabolismo do Instituto de Medicina Molecular da Universidade de Lisboa, Lisboa, Portugal (CSG); the Escola Superior de Tecnologia da Saúde de Lisboa, Lisboa, Portugal (BC, SG, EC, and MB); and the Serviço de Gastrenterologia do Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE, Lisboa, Portugal (PF, CNL, and MC)

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 µg/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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