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- W1574209969 abstract "15036 Background: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the folate metabolism pathway. Two common genetic polymorphisms (C677T and A1298C) are associated with reduced MTHFR activity. The aim of our study was to analyze the distribution of C677T and A1298C MTHFR gene polymorphisms in colorectal cancer (CRC) patients (pts), to evaluate their role as predictive markers of 5-FU toxicity in adjuvant chemotherapy. Methods: Genomic DNA was isolated from peripheral blood lymphocytes of 23 pts, using Puregene Genomic DNA Purification System. Pts (9 M/14 F) with histologically confirmed CRC, were treated with 5-FU containing adjuvant therapy. Median age was 61.5 (range 39–75). Genotyping for MTHFR polymorphism was carried out by DG-DGGE (double gradient-denaturing gradient gel electrophoresis). Results: The distribution of MTHFR T677 mutated allele in our population was 41.3%. Genotype frequencies were 47.8% for heterozygous CT677, 34.8% for the wild-type CC677 and 17.4% for the homozygous mutated TT677. The prevalence of MTHFR C1298 mutated allele was 28.3%, while genotype distribution was 56.5% for the wild-type AA1298, 30.4% for the heterozygous AC1298, and 13.1% for the homozygous mutated CC1298. The multivariate analysis for the combined polymorphisms showed that pts with double heterozygous genotype CT677/AC1298 were 21.7% in the sample population. The frequencies of other combined genotypes were 26.1% for CT677/AA1298 genotype, 17.4% for TT677/AA1298, 13.1% for both CC677/CC1298 and CC677/AA1298, and 8.7% for CC677/AC1298. We recorded severe G3-G4 toxicities after the initial administrations of chemotherapy in 3/4 pts with MTHFR genotype TT 677/AA1298 (G3 granulocytopenia and dyarrhea in 1/3 pts, G3 mucositis in 1/3 pts, and G3 thrombocytopenia in 1/3 pts). Mild toxicities were observed in pts having different genotypes. Conclusions: Our preliminary data show that the TT677 MTHFR genotype influences the development of 5-FU toxicity. Further studies will be carried out to evaluate the role of MTHFR polymorphisms as predictive markers of acute toxicity. DG-DGGE analysis used for MTHFR genotyping was proved to be a fast and reliable method helpful for pre- treatment screening. No significant financial relationships to disclose." @default.
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- W1574209969 date "2008-05-20" @default.
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- W1574209969 title "Role of MTHFR polymorphisms as predictive markers of acute toxicity during 5-fluorouracil based chemotherapy for colorectal cancer: Preliminary data" @default.
- W1574209969 doi "https://doi.org/10.1200/jco.2008.26.15_suppl.15036" @default.
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