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Gender-dependent association of TYMS-TSER polymorphism with 5-fluorouracil or capecitabine-based chemotherapy toxicity

    Charalampia Ioannou

    Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, 68100, Greece

    ,
    Georgia Ragia

    Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, 68100, Greece

    ,
    Ioanna Balgkouranidou

    Department of Medical Oncology, University General Hospital of Alexandroupolis, Medical School, Democritus University of Thrace, Alexandroupolis, 68100, Greece

    ,
    Nikolaos Xenidis

    Department of Medical Oncology, University General Hospital of Alexandroupolis, Medical School, Democritus University of Thrace, Alexandroupolis, 68100, Greece

    ,
    Kyriakos Amarantidis

    Department of Medical Oncology, University General Hospital of Alexandroupolis, Medical School, Democritus University of Thrace, Alexandroupolis, 68100, Greece

    ,
    Triantafyllia Koukaki

    Department of Medical Oncology, University General Hospital of Alexandroupolis, Medical School, Democritus University of Thrace, Alexandroupolis, 68100, Greece

    ,
    Eirini Biziota

    Department of Medical Oncology, University General Hospital of Alexandroupolis, Medical School, Democritus University of Thrace, Alexandroupolis, 68100, Greece

    ,
    Stylianos Kakolyris

    Department of Medical Oncology, University General Hospital of Alexandroupolis, Medical School, Democritus University of Thrace, Alexandroupolis, 68100, Greece

    &
    Vangelis G Manolopoulos

    *Author for correspondence: Tel.: +30 2551 030 523;

    E-mail Address: emanolop@med.duth.gr

    Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, 68100, Greece

    Clinical Pharmacology & Pharmacogenetics Unit, Academic General Hospital of Alexandroupolis, Alexandroupolis, Greece

    Published Online:https://doi.org/10.2217/pgs-2021-0031

    Aim:TYMS gene encodes for TS enzyme involved in 5-fluorouracil (5-FU) and capecitabine (CAP) metabolism. This study assessed the association of TYMS-TSER and 3RG>C polymorphisms with 5-FU/CAP adverse event (AE) incidence. Materials & methods:TYMS-TSER and 3RG>C polymorphisms were analyzed by use of PCR/PCR-RFLP in 313 5-FU/CAP-treated cancer patients. Results: Female TYMS-TSER 2R carriers were at increased risk for 5-FU/CAP AEs (odds ratio: 2.195; p = 0.032). 2R/2R genotype was the only factor that increased risk for delayed drug administration or therapy discontinuation (odds ratio: 5.049; p = 0.016). No other associations were found. Conclusion:TYMS-TSER 3R/2R polymorphism was associated with incidence of AEs in female cancer patients. This gender-driven association potentially implicates the ER that, in female patients, potentially regulates TS expression.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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