title: 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.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  These results show an association between the C677T MTHFR variant and different folate intakes on risk of CRC.
authors.affiliation: Escola Superior de Tecnologia da Saúde de Lisboa, Unidade de Nutrição e Metabolismo do Instituto de Medicina Molecular da Universidade de Lisboa, Lisboa, Portugal. catarina.guerreiro@estesl.ipl.pt
authors.forename: Catarina Sousa
authors.initials: CS
authors.lastname: Guerreiro
authors.forename: Bruno
authors.initials: B
authors.lastname: Carmona
authors.forename: Susana
authors.initials: S
authors.lastname: Gonçalves
authors.forename: Elisabete
authors.initials: E
authors.lastname: Carolino
authors.forename: Paulo
authors.initials: P
authors.lastname: Fidalgo
authors.forename: Miguel
authors.initials: M
authors.lastname: Brito
authors.forename: Carlos Nobre
authors.initials: CN
authors.lastname: Leitão
authors.forename: Marília
authors.initials: M
authors.lastname: Cravo
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000378:metabolism; D005838:Genotype; D012696:Glycine Hydroxymethyltransferase / Q000235:genetics*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D012696:Glycine Hydroxymethyltransferase