Methylenetetrahydrofolate reductase gene polymorphisms: genomic predictors of clinical response to fluoropyrimidine-based chemotherapy?

Cancer Chemother Pharmacol. 2006 Jun;57(6):835-40. doi: 10.1007/s00280-005-0089-1. Epub 2005 Sep 27.


Fluorouracil (5-FU) is widely used in the treatment of colorectal cancer. Methylenetetrahydrofolate reductase (MTHFR) may play a central role in the action of 5-FU, an inhibitor of thymidylate synthase, by converting 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. The aim of this study was to ascertain whether two polymorphisms in the MTHFR gene (677C>T and 1298 A>C) could be used as genomic predictors of clinical response to fluoropyrimidine-based chemotherapy (in combination with irinotecan or oxaliplatin). Ninety-four patients diagnosed with metastatic colorectal cancer and undergoing 5-FU-containing chemotherapy as a first line treatment were studied. The results suggest that the MTHFR genotype cannot be considered as an independent factor of outcome in colorectal cancer patients under 5-FU-based chemotherapy.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality
  • Disease-Free Survival
  • Female
  • Fluorouracil / therapeutic use*
  • Humans
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Middle Aged
  • Pharmacogenetics
  • Polymorphism, Genetic
  • Thymidylate Synthase / antagonists & inhibitors


  • Antimetabolites, Antineoplastic
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Thymidylate Synthase
  • Fluorouracil