title: Impact of the MTHFR C677T polymorphism on colorectal cancer in a population with low genetic variability.
abstract: OBJECTIVE
  Methylenetetrahydrofolate reductase (MTHFR) plays a key role in folate metabolism, and folate is implicated in carcinogenesis by its role in DNA methylation, repair, and synthesis. We analyzed the impact of MTHFR C677T polymorphism in colorectal cancer in a region of the Tenerife Island whose population has a history of genetic isolation and a low genetic variability. This allows analyzing the effects of the polymorphism that are not due to interactions with different genetic variants.
  
  
  METHODS
  Genomic DNA of 50 Spanish sporadic colorectal cancer (CRC) patients and 103 controls was analyzed by PCR/RFLP and sequencing.
  
  
  RESULTS
  The T allele is more frequent in controls than in patients (P < 0.01). The variant (T) carriers displayed significant odds ratio values for the CT heterozygotes (P = 0.026) and even when grouping heterozygote (CT) and homozygotes (TT) (P = 0.015). Patients carriers of the variant T (CT y TT) show a higher survival rate after chemotherapy than the CC homozygotes (log rank; P = 0.001).
  
  
  CONCLUSIONS
  The MTHRF C677T variant has a protective effect on CRC development in a population with low allelic variability and an optimal intake of folic acid. Moreover, patients carrying the variant (T) show a better prognosis after 5-fluorouracil/folinic acid-based chemotherapy.
authors: Servicio de Cirugía General y Digestiva, Hospital Universitario de Canarias, Ofra, s/n. La Cuesta, 38320, La Laguna, Santa Cruz de Tenerife, Islas Canarias, Spain. luciano_delgado1@yahoo.es
authors: Luciano
authors: L
authors: Delgado-Plasencia
authors: Vicente
authors: V
authors: Medina-Arana
authors: Alberto
authors: A
authors: Bravo-Gutiérrez
authors: Julián
authors: J
authors: Pérez-Palma
authors: Hugo
authors: H
authors: Álvarez-Argüelles
authors: Eduardo
authors: E
authors: Salido-Ruiz
authors: Antonia M
authors: AM
authors: Fernández-Peralta
authors: Juan J
authors: JJ
authors: González-Aguilera
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
chemical_list: C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)