Fluoropyrimidine-based chemotherapy is extensively used for the treatment of solid cancers, including colorectal cancer. However, fluoropyrimidine-driven toxicities are a major problem in the management of the disease. The grade and type of the toxicities depend on demographic factors, but substantial inter-individual variation in fluoropyrimidine-related toxicity is partly explained by genetic factors. The aim of this study was to investigate the effect of dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), and methylenetetrahydrofolate reductase (MTHFR)
polymorphisms in colorectal cancer patients. Eighty-five patients who were administered fluoropyrimidine-based treatment were included in the study. The DPYD
polymorphisms were scanned by a next generation Sequenom MassARRAY. Fluoropyrimidine toxicities were observed in 92% of all patients. The following polymorphisms were detected: DPYD
85T>C (29.4% heterozygote mutants, 7.1% homozygote mutants), DPYD
IVS 14+1G>A (1.2% heterozygote mutants), TYMS
1494del TTAAAG (38.4% heterozygote mutants, 24.7% homozygote mutants), MTHFR
677C>T (43.5% heterozygote mutants, 9.4% homozygote mutants) and MTHFR
1298A>C (8.2% heterozygote mutants, 2.4% homozygote mutants). A statistically significant association was demonstrated between MTHFR
677C>T and fluoropyrimidine-related toxicity (p
value = 0.007). Furthermore, MTHFR
1298A>C was associated with hematopoietic toxicity (p
value = 0.008). MTHFR
polymorphisms may be considered as related factors of fluoropyrimidine toxicity and may be useful as predictive biomarkers for the determination of the colorectal cancer patients who can receive the greatest benefit from fluoropyrimidine-based treatments.
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