Gender-Dependent Association of <i>Tyms</i> -TSER Polymorphism With 5-Fluorouracil or Capecitabine-Based Chemotherapy Toxicity

Abstract

<b>Aim:</b><i>TYMS</i> gene encodes for TS enzyme involved in 5-fluorouracil (5-FU) and capecitabine (CAP) metabolism. This study assessed the association of <i>TYMS</i>-TSER and 3RG>C polymorphisms with 5-FU/CAP adverse event (AE) incidence. <b>Materials & methods:</b><i>TYMS</i>-TSER and 3RG>C polymorphisms were analyzed by use of PCR/PCR-RFLP in 313 5-FU/CAP-treated cancer patients. <b>Results:</b> Female <i>TYMS</i>-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. <b>Conclusion:</b><i>TYMS</i>-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.