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J. Pers. Med. 2018, 8(4), 45; https://doi.org/10.3390/jpm8040045

DPYD, TYMS and MTHFR Genes Polymorphism Frequencies in a Series of Turkish Colorectal Cancer Patients

1
Biomedical Center, Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland
2
Cell Biology Unit, Department of Pathology, Landspitali University Hospital, 101 Reykjavik, Iceland
3
Department of Basic Oncology, Institute of Oncology, Dokuz Eylul University, 35350 Izmir, Turkey
4
Personalized Medicine and Pharmacogenomics/Genomics Research Centre-BIFAGEM, 35350 Izmir, Turkey
5
Bozyaka Education and Research Hospital, Division of Medical Oncology, Department of Internal Medicine, Health Science University, 35170 Izmir, Turkey
6
Department of Preventive Oncology, Institute of Oncology, Dokuz Eylul University, 35350 Izmir, Turkey
7
Department of Medical Informatics and Biostatistics, Faculty of Medicine, Dokuz Eylul University, 35350 Izmir, Turkey
8
Department of Clinical Oncology, Faculty of Medicine, Dokuz Eylul University, 35350 Izmir, Turkey
9
Department of Translational Oncology, Institute of Oncology, Dokuz Eylul University, 35350 Izmir, Turkey
*
Author to whom correspondence should be addressed.
Received: 19 October 2018 / Revised: 28 November 2018 / Accepted: 10 December 2018 / Published: 13 December 2018
(This article belongs to the Special Issue Biomarkers in Colorectal Cancer)
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Abstract

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, TYMS and MTHFR 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. View Full-Text
Keywords: DPYD; TYMS and MTHFR genes; polymorphisms; pharmacogenetics; colorectal cancer DPYD; TYMS and MTHFR genes; polymorphisms; pharmacogenetics; colorectal cancer
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Amirfallah, A.; Calibasi Kocal, G.; Unal, O.U.; Ellidokuz, H.; Oztop, I.; Basbinar, Y. DPYD, TYMS and MTHFR Genes Polymorphism Frequencies in a Series of Turkish Colorectal Cancer Patients. J. Pers. Med. 2018, 8, 45.

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