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.


CONCLUSIONS
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.
Kim
Suk-Ran
SR
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Park
Chang-Hun
CH
Park
Silvia
S
Park
Joon-Oh
JO
Lee
Jeeyun
J
Lee
Soo-Youn
SY
D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects* / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020258:Neurotoxicity Syndromes / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics; D011110:Polymorphism, Genetic; D017384:Sequence Deletion; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics; D013940:Thymidylate Synthase / Q000235:genetics*
D000964:Antimetabolites, Antineoplastic; D013940:Thymidylate Synthase; D005472:Fluorouracil