Expression of genes for 5-FU-metabolizing enzymes and response to irinotecan plus 5-FU-leucovorin in colorectal cancer.
BACKGROUND
5-Fluorouracil (5-FU) is initially catabolized by dihydropyrimidine dehydrogenase. Thymidylate synthase (TS) is the target enzyme of 5-FU. In addition, activation of 5-FU to form various nucleotides via three pathways requires phosphorylation by orotate phosphoribosyltransferase, thymidine phosphorylase and uridine phosphorylase, respectively. The aim of this study was to assess the predictive value of the expression of these genes in patients receiving irinotecan plus 5-FU/leucovorin therapy (IFL) for colorectal cancer.


METHODS
Twenty-seven patients with metastatic, or recurrent colorectal cancer were studied. Enzyme gene expression was measured in primary tumors by the real-time reverse transcription PCR method.


RESULTS
The TS mRNA level was significantly higher in the responders than in the non-responders (p=0.0409).


CONCLUSIONS
The effect of IFL therapy may be determined by the extent of TS mRNA expression. It is suggested that assay of TS mRNA may be useful for predicting the effect of intravenous regimens such as FOLFIRI.
Noda
Eiji
E
Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-5-7Asahimachi Abeno-ku, Osaka, 545-8585, Japan.
Maeda
Kiyoshi
K
Inoue
Toru
T
Nishihara
Tamahiro
T
Nishiguchi
Yukio
Y
Ohira
Masaichi
M
Hirakawa
Kosei
K
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015870:Gene Expression; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D009962:Orotate Phosphoribosyltransferase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013939:Thymidine Phosphorylase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D013940:Thymidylate Synthase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014543:Uridine Phosphorylase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D000077146:Irinotecan; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase; D014543:Uridine Phosphorylase; D013939:Thymidine Phosphorylase; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin