title: Methylenetetrahydrofolate reductase 677 C-->T polymorphism and risk of proximal colon cancer in north Italy.
abstract: OBJECTIVE
  Gene silencing by hypermethylation plays an important role in proximal colon carcinogenesis. Conversely, DNA hypomethylation has been associated with distal colon cancer (CLC). Methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of 5',10'-methylenetetrahydrofolate to 5'-methyl tetrahydrofolate, which serves as methyl donor in the remethylation of homocysteine to methionine. A common MTHFR 677 C-->T polymorphism is characterized by reduced catalytic activity, which affects methionine synthesis and DNA methylation. The aim of the study was to investigate the role of MTHFR 677 C-->T gene polymorphism in the tumorigenesis of proximal and distal CLC in a monoinstitutional group of patients in North Italy.
  
  
  METHODS
  One-hundred thirty four consecutive proximal and 142 consecutive distal CLC patients, and 279 control subjects without cancer were genotyped for MTHFR using PCR-restriction fragment-length polymorphism analysis.
  
  
  RESULTS
  The prevalence of the 677 TT genotype was significantly (P = 0.005) lower in patients with proximal tumors (10 of 134, 7%) than in subjects with distal tumors (28 of 142, 20%). Case/control approach indicated that individuals homozygous for the 677 TT allele had a significantly reduced risk (2.8-fold) (adjusted odds ratio, 0.36; 95% confidence intervals, 0.14-0.91) of developing proximal CLC compared with those harboring the wild-type or heterozygous genotype (677 CC or 677 CT). No significant association between CLC risk and TT genotype was observed in patients with distal tumors (odds ratio, 1.01; 95% confidence interval, 0.48-2.14).
  
  
  CONCLUSIONS
  Our findings support a role for MTHFR 677 TT genotype in reducing proximal CLC risk in North Italy.
authors.affiliation: Experimental and Clinical Pharmacology Unit, Division of Experimental Oncology 1, Centro di Riferimento Oncologico, Aviano (PN), Italy. gtoffoli@cro.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Toffoli
authors.forename: Roberta
authors.initials: R
authors.lastname: Gafà
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lanza
authors.forename: Riccardo
authors.initials: R
authors.lastname: Dolcetti
authors.forename: Franca
authors.initials: F
authors.lastname: Sartor
authors.forename: Massimo
authors.initials: M
authors.lastname: Libra
authors.forename: Alessandra
authors.initials: A
authors.lastname: Viel
authors.forename: Mauro
authors.initials: M
authors.lastname: Boiocchi
mesh_terms: D000483:Alleles; D003110:Colonic Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D003596:Cytosine; D019175:DNA Methylation; D020868:Gene Silencing; D005838:Genotype; D006801:Humans; D007558:Italy / Q000453:epidemiology; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012016:Reference Values; D012307:Risk Factors; D013941:Thymine
chemical_list: D003596:Cytosine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013941:Thymine