4.7 Article

MTHFR polymorphisms and 5-FU-based adjuvant chemotherapy in colorectal cancer

Journal

ANNALS OF ONCOLOGY
Volume 20, Issue 10, Pages 1660-1666

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/annonc/mdp046

Keywords

colorectal cancer; 5-fluorouracil; methylenetetrahydrofolate reductase; pharmacogenetics; single-nucleotide polymorphisms

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Funding

  1. Faculty of Health Sciences, University of Copenhagen

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Patients and methods: We included 331 patients who had been treated with adjuvant 5-FU/leucovorin chemotherapy after intended curative resection between 1997 and 2003. Clinical data, including relapse rates, overall survival, and tumor stage, were collected. DNA was extracted from formalin-fixed tumor tissue and analyzed for the MTHFR 677C > T and 1298A > C SNPs with real-time PCR. Results: The MTHFR 677C > T and 1298A > C polymorphisms were not associated with survival or relapse-free survival (P > 0.2). The 677 CC genotype was associated to toxicity (odds ratio = 1.83, P = 0.01). Conclusions: The MTHFR 677C > T and 1298A > C polymorphisms probably do not predict efficacy of adjuvant 5-FU treatment in colorectal cancer after complete resection; however, the 677C > T polymorphism may be associated with lower toxicity in 5-FU treatment. Implementation of SNP analysis for these polymorphisms for individualized treatment is premature.

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