Gender-dependent association of TYMS-TSER polymorphism with 5-fluorouracil or capecitabine-based chemotherapy toxicity.
Charalampia IoannouGeorgia RagiaIoanna BalgkouranidouNikolaos XenidisKyriakos AmarantidisTriantafyllia KoukakiEirini BiziotaStylianos KakolyrisVangelis G ManolopoulosPublished in: Pharmacogenomics (2021)
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.
Keyphrases
- locally advanced
- end stage renal disease
- newly diagnosed
- risk factors
- chronic kidney disease
- ejection fraction
- mental health
- drug administration
- poor prognosis
- phase ii study
- genome wide
- oxidative stress
- squamous cell carcinoma
- copy number
- radiation therapy
- gene expression
- rectal cancer
- patient reported outcomes
- metastatic colorectal cancer
- binding protein
- phase iii
- smoking cessation
- genome wide analysis