title: Genetic polymorphisms in MTHFR (C677T, A1298C), MTR (A2756G) and MTRR (A66G) genes associated with pathological characteristics of prostate cancer in the Ecuadorian population.
abstract: BACKGROUND
  The methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and MTR reductase (MTRR) enzymes act in the folate metabolism, which is essential in methylation and synthesis of nucleic acids. The single nucleotide polymorphisms, MTHFR C677T, A1298C, MTR A2756G and MTRR A66G, cause alteration in the homocysteine levels and reduced enzymatic activity that generates deficiency in the assimilation of folates associated with DNA damage; that is, why it is important to know if the single nucleotide polymorphisms are associated with the pathological characteristics and development of prostate cancer, through a case-control retrospective study.
  
  
  METHODS
  DNA was extracted from 110 healthy and 104 affected men. The genotypes were determined by means of the polymerase chain reaction-restriction fragment length polymorphism and confirmed with genomic sequencing.
  
  
  RESULTS
  We found significant association between the genotypes of the MTHFR C677T polymorphism: C/T (odds ratio [OR] = 2.2; 95% confidence interval [CI] = 1.3-3.9; P = 0.008) and C/T + T/T (OR = 2.2; 95% CI = 1.3-3.9; P = 0.009) with the risk of prostate cancer development, and a slight association with MTRR A66G. Regarding pathological characteristics, we found significant risk between the C/T + T/T genotypes and the Gleason score (7-10) of poorly differentiated carcinoma (OR = 5.2; 95% CI = 1.7-16.2; P = 0.007). On the other hand, a significant association between A1298C, A66G, and A2756G with the pathological characteristics was not found (P > 0.05).
  
  
  CONCLUSIONS
  The MTHFR C677T polymorphism has significant effects on susceptibility to prostate cancer in Ecuadorian population, especially with the Gleason grade.
authors: Biomedical Research Institute (AL-C, GJ-K, MJM, AC, CE, CPM), School of Health Science, Universidad De Las Américas, Quito, Ecuador; Department of Pathology (FR), Solon Espinoza Ayala Oncologic Hospital, Quito, Ecuador; and Department of Pathology (NV), Carlos Andrade Marin Hospital, Quito, Ecuador.
authors: Andrés
authors: A
authors: López-Cortés
authors: Gabriela
authors: G
authors: Jaramillo-Koupermann
authors: María J
authors: MJ
authors: Muñoz
authors: Alejandro
authors: A
authors: Cabrera
authors: Carolina
authors: C
authors: Echeverría
authors: Felipe
authors: F
authors: Rosales
authors: Nicolás
authors: N
authors: Vivar
authors: César
authors: C
authors: Paz-y-Miño
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004484:Ecuador / Q000453:epidemiology; D005287:Ferredoxin-NADP Reductase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D012189:Retrospective Studies
chemical_list: C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; C585801:MTR protein, human