Impact of the MTHFR C677T polymorphism on colorectal cancer in a population with low genetic variability

Int J Colorectal Dis. 2013 Sep;28(9):1187-93. doi: 10.1007/s00384-013-1644-6. Epub 2013 Feb 20.


Purposes: 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.

MeSH terms

  • Amino Acid Substitution / genetics*
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / enzymology*
  • Colorectal Neoplasms / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Risk Factors


  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)