| Autor: |
Khushman, Moh’d, Patel, Girijesh Kumar, Maharjan, Anu Singh, McMillin, Gwendolyn A., Nelson, Cindy, Hosein, Peter, Singh, Ajay P. |
| Zdroj: |
The Pharmacogenomics Journal; June 2021, Vol. 21 Issue: 3 p308-317, 10p |
| Abstrakt: |
Introduction: The prevalence of 2R/2R TYMSgenotype is variable but estimated to be around 20–30% in Caucasians. The clinical relevance of TYMS 2R/2Rgenotype in predicting severe fluoropyrimidine-related adverse events (FrAE) is controversial. Here, we explored the prevalence and clinical relevance of 2R/2R TYMSgenotype. Methods: Between 2011 and 2018, 126 patients were genotyped for TYMS. FrAEs were graded according to CTCAE version 5.0. Fisher’s exact test was used for statistical analysis. Results: The prevalence of TYMS 2R/2Rgenotype was 24.6%. Among patients with TYMS genotypes (N= 71) that predict decreased TS expression, 2R/2R TYMSgenotype was the most common TYMSgenotype seen in female (57%) and African American (60%) patients. Among patients with genotypes that predict increased TS expression (N= 55), 12 patients had grade 3–4 FrAEs (22%), while among patients with genotypes that predict decreased TS expression (N= 71), 30 patients had grade 3–4 FrAEs (42%) (p= 0.0219). Compared to patients with genotypes predicting increased TS expression, 17 out of 31 patients (55%) with TYMS 2R/2Rgenotype had grade 3–4 FrAEs (p= 0.0039) and 15 out 40 patients (38%) with TYMS 2R/3RCand TYMS 3RC/3RCgenotype had grade 3–4 FrAEs (p= 0.1108). Conclusion: The prevalence of TYMS 2R/2Rgenotype was 24.6%, and it had a unique sex and ethnic distribution. Polymorphism in the promoter region of TYMSgene that predicts decreased TS expression due to 2R/2Rvariant was associated with grade 3–4 FrAEs. These data suggest that genotyping patients who are not DPD deficient for TYMS might identify patients at risk of severe FrAEs. |
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