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Cancer Chemother Pharmacol. 2006 Jun;57(6):835-40. Epub 2005 Sep 27.

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

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Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Avda. S. Antoni M. Claret 167, 08025, Barcelona, Spain.


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.

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