scholarly journals Elevated levels of mRNAs encoding dihydropyrimidine dehydrogenase and thymidylate synthase are associated with improved survival of patients with hepatocellular carcinoma treated with S-1

2017 ◽  
Vol 14 (1) ◽  
pp. 930-936 ◽  
Author(s):  
Yusuke Okano ◽  
Hidekazu Kuramochi ◽  
Go Nakajima ◽  
Satoshi Katagiri ◽  
Masakazu Yamamoto
Keyword(s):  
Hepatocellular Carcinoma ◽  
Thymidylate Synthase ◽  
Dihydropyrimidine Dehydrogenase

Significance of dihydropyrimidine dehydrogenase and thymidylate synthase mRNA expressions in hepatocellular carcinoma

2009 ◽  
Vol 39 (3) ◽  
pp. 274-281 ◽  
Author(s):  
Akira Nii ◽  
Mitsuo Shimada ◽  
Toru Ikegami ◽  
Yukari Harino ◽  
Satoru Imura ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Thymidylate Synthase ◽  
Dihydropyrimidine Dehydrogenase

Germline pharmacogenomics of thymidylate synthase gene in patients with gastrointestinal malignancies treated with fluoropyrimidines-based chemotherapy regimens.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 545-545 ◽  
Author(s):  
Saad Awan ◽  
Girijesh K. Patel ◽  
Anu Singh Maharjan ◽  
Gwendolyn A. McMillin ◽  
William R. Taylor ◽  
...  
Keyword(s):  
Thymidylate Synthase ◽  
Promoter Region ◽  
Active Metabolite ◽  
Dihydropyrimidine Dehydrogenase ◽  
S Phase ◽  
Gastrointestinal Malignancies ◽  
Exact Test ◽  
Racial Background ◽  
Dehydrogenase Gene ◽  
Grade 3

545 Background: Fluoropyrimidines are antimetabolites that target the S phase of the cell cycle. The active metabolite, 5-fluorodeoxyuridine monophosphate inhibits thymidylate synthase (TS) enzyme, thus preventing DNA synthesis and ultimately cell death. While controversy exists in the literature, polymorphism in the promoter region of thymidylate synthase gene (TYMS) that decrease TS expression has been associated with increased fluoropyrimidines-associated toxicities. This study explored the association between polymorphism in the promoter region of TYMS gene and fluoropyrimidines-associated toxicities in patients with gastrointestinal malignancies with mixed racial background. Methods: Between 2011 and 2018, 126 patients were genotyped for TYMS. Patients with known high-risk dihydropyrimidine dehydrogenase gene variants were excluded. Fluoropyrimidines-associated toxicity was graded according to the National Cancer Institiute Common Terminology Criteria for Adverse Events (v 5.0). Fisher’s exact test was used for statistical analysis. Results: TYMS genotypes that predict increased TS expression (3RG/3RG, 3RG/3RC, 2R/3RG, 2R/4R, 3R/4R, 4R/3RG) were identified in 55 patients (44%). TYMS genotypes that predict decreased TS expression (2R/2R, 2R/3RC, 3RC/3RC) were seen in 71 patients (56%). Among patients with genotypes that predict increased TS expression (N = 55), 12 patients had grade 3-4 toxicity (22%) while among patients with genotypes that predict decreased TS expression, 30 patients had grade 3-4 toxicities (42%) (P = 0.0219). Compared to patients with genotypes predicting increased TS expression, 17 out of 31 patients (55%) with 2R/2R TYMS genotype had grade 3-4 toxicity (P = 0.0039) and 15 out 40 patients (38%) with 2R/3RC and 3RC/3RC TYMS genotype had grade 3-4 toxicity (P = 0.1108). Among patients with 2R/2R TYMS, Caucasians represented 61% and African Americans represented 39%. Females represented 65% of the patients. Conclusions: Polymorphism in the promoter region of TYMS gene that predict decreased TS expression due to 2R/2R variant was associated with grade 3-4 fluoropyrimidines-associated toxicities.

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