Genetic polymorphisms associated with 5-Fluorouracil-induced neurotoxicity.

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.