BACKGROUND: Encephalopathy is a rare drug toxicity of fluorouracil therapy. Toxicity from fluorouracil therapy is known to be associated with the individual genetic background of the enzymes, thymidylate synthase and dihydropyrimidine dehydrogenase. METHODS: Two patients with advanced gastric cancer and metastatic pancreatic cancer who received 5-fluorouracil-based chemotherapy presented with acute mental change and hyperammonemia. To evaluate the genetic background of the fluorouracil-associated hyperammonemic encephalopathy, analysis of the polymorphisms of the TYMS, DPYD and MTHFR genes was performed. RESULTS: The patients revealed to be TYMS suppressors showing homogenous deletion of 6 bp in the 3'-UTR and 3RC/3RC genotype in the promoter enhancer region (TSER), respectively. CONCLUSION: Genetic polymorphisms of the TYMS gene would contribute to the 5-fluorouracil-associated hyperammonemic encephalopathy. The prospective validation of the clinical implication of TYMS gene polymorphisms is warranted.
BACKGROUND:Encephalopathy is a rare drug toxicity of fluorouracil therapy. Toxicity from fluorouracil therapy is known to be associated with the individual genetic background of the enzymes, thymidylate synthase and dihydropyrimidine dehydrogenase. METHODS: Two patients with advanced gastric cancer and metastatic pancreatic cancer who received 5-fluorouracil-based chemotherapy presented with acute mental change and hyperammonemia. To evaluate the genetic background of the fluorouracil-associated hyperammonemic encephalopathy, analysis of the polymorphisms of the TYMS, DPYD and MTHFR genes was performed. RESULTS: The patients revealed to be TYMS suppressors showing homogenous deletion of 6 bp in the 3'-UTR and 3RC/3RC genotype in the promoter enhancer region (TSER), respectively. CONCLUSION: Genetic polymorphisms of the TYMS gene would contribute to the 5-fluorouracil-associated hyperammonemic encephalopathy. The prospective validation of the clinical implication of TYMS gene polymorphisms is warranted.
Authors: Soma Ghosh; M Zulfiquer Hossain; Michael Borges; Michael G Goggins; Roxann G Ingersoll; James R Eshleman; Alison P Klein; Scott E Kern Journal: PLoS One Date: 2012-04-05 Impact factor: 3.240