Dataset Information

The prevalence and clinical relevance of 2R/2R TYMS genotype in patients with gastrointestinal malignancies treated with fluoropyrimidine-based chemotherapy regimens.

ABSTRACT:

Introduction

The prevalence of 2R/2R TYMS genotype is variable but estimated to be around 20-30% in Caucasians. The clinical relevance of TYMS 2R/2R genotype in predicting severe fluoropyrimidine-related adverse events (FrAE) is controversial. Here, we explored the prevalence and clinical relevance of 2R/2R TYMS genotype.

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/2R genotype was 24.6%. Among patients with TYMS genotypes (N = 71) that predict decreased TS expression, 2R/2R TYMS genotype was the most common TYMS genotype 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/2R genotype had grade 3-4 FrAEs (p = 0.0039) and 15 out 40 patients (38%) with TYMS 2R/3RC and TYMS 3RC/3RC genotype had grade 3-4 FrAEs (p = 0.1108).

Conclusion

The prevalence of TYMS 2R/2R genotype was 24.6%, and it had a unique sex and ethnic distribution. Polymorphism in the promoter region of TYMS gene that predicts decreased TS expression due to 2R/2R variant 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.

SUBMITTER: Khushman M

PROVIDER: S-EPMC8159739 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Publications

The prevalence and clinical relevance of 2R/2R TYMS genotype in patients with gastrointestinal malignancies treated with fluoropyrimidine-based chemotherapy regimens.

Khushman Moh'd M Patel Girijesh Kumar GK Maharjan Anu Singh AS McMillin Gwendolyn A GA Nelson Cindy C Hosein Peter P Singh Ajay P AP

The pharmacogenomics journal 20210219 3

<h4>Introduction</h4>The prevalence of 2R/2R TYMS genotype is variable but estimated to be around 20-30% in Caucasians. The clinical relevance of TYMS 2R/2R genotype in predicting severe fluoropyrimidine-related adverse events (FrAE) is controversial. Here, we explored the prevalence and clinical relevance of 2R/2R TYMS genotype.<h4>Methods</h4>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 statistic ...[more]

PMID: 33608662

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Dataset Information

The prevalence and clinical relevance of 2R/2R TYMS genotype in patients with gastrointestinal malignancies treated with fluoropyrimidine-based chemotherapy regimens.

Introduction

Methods

Results

Conclusion

Publications

The prevalence and clinical relevance of 2R/2R TYMS genotype in patients with gastrointestinal malignancies treated with fluoropyrimidine-based chemotherapy regimens.

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