title: Gene polymorphisms MTHFRC677T and MTRA2756G as predictive factors in adjuvant chemotherapy for stage III colorectal cancer.
abstract: BACKGROUND
  The aim of this study was to explore the effect in stage III colorectal cancer of functional gene polymorphisms methylenetetrahydrofolate reductase (MTHFR C677T) and methionine synthase (A2756G), in the folate metabolism on outcome and risk of toxicity for adjuvant chemotherapy. A secondary aim was to investigate any possible interdependency between the two genes.
  
  
  METHODS
  one hundred and fifty randomly chosen patients with stage III colorectal cancer, treated with adjuvant chemotherapy, were genotyped by real-time PCR. Patient and treatment data were retrieved and assessed for demography, pathology, chemotherapy tolerability and survival after adjuvant therapy. The polymorphisms were studied separately and in combination to discover possible interactions.
  
  
  RESULTS
  Patients with MTHFR 677 CC genotype carried lower risks of suffering from nausea (p=0.027), parasthesia (p=0.0042) and need for dose reduction (p=0.025). The CC genotype was also associated with better survival (p<0.034). There was interdependency with MTR A2756G. Patients with MTR AG/GG in combination with MTHFR CT/TT genotypes carried the highest risk of side-effects.
  
  
  CONCLUSIONS
  Functional polymorphisms of MTHFR C677T and MTR A2756G can affect outcome and risk of toxicity during adjuvant chemotherapy in stage III colorectal cancer. Their possible interdependence brings attention to the function of folate metabolism overall regarding its association with 5-fluoruracil related toxicity. Our results could explain some of the difficulties of obtaining reproducible and uniform results when using single polymorphisms as predictive markers.
authors.affiliation: Department of Surgery, Sahlgrenska University Hospital Östra, 41685 Gothenburg, Sweden. helena.taflin@vgregion.se
authors.forename: Helena
authors.initials: H
authors.lastname: Taflin
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Wettergren
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Odin
authors.forename: Göran
authors.initials: G
authors.lastname: Carlsson
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Derwinger
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase