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Thymidylate synthase and dihydropyrimidine dehydrogenase mRNA expression after administration of 5‐fluorouracil to patients with colorectal cancer
Author(s) -
Mauritz Robert,
van Groeningen Cees J.,
Smid Kees,
Jansen Gerrit,
Pinedo Herbert M.,
Peters Godefridus J.
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22626
Subject(s) - thymidylate synthase , dihydropyrimidine dehydrogenase , fluorouracil , colorectal cancer , cancer research , messenger rna , oncology , medicine , biology , cancer , genetics , gene
This study explores the effect of 5‐fluorouracil (5FU) exposure on mRNA levels of its target enzyme thymidylate synthase (TS) and the rate‐limiting catabolic enzyme dihydropyrimidine dehydrogenase (DPD) in tumors of colorectal cancer patients. TS and DPD mRNA levels were determined in primary tumor and liver metastasis samples from patients who were either not pretreated ( n = 29) or given one presurgery bolus of 5FU ( n = 67). In both groups a wide variation in TS mRNA levels was observed. Median TS mRNA expression in 17 primary tumors of exposed patients was 3.0‐fold higher than in 19 primary tumors of unexposed patients ( p = 0.015). TS mRNA expression in liver metastasis samples of exposed patients ( n = 16) was also higher (5.2‐fold) than that of unexposed patients ( n = 48; p < 0.001). Also DPD mRNA expression displayed a large degree of interpatient variation. No difference in DPD expression in liver metastasis samples was observed between exposed and unexposed patients. However, median DPD mRNA expression in 15 primary tumors of exposed patients was 3.2‐fold lower than in 18 primary tumors of unexposed patients ( p = 0.027). In conclusion, administration of 5FU in vivo influences the gene expression of TS and DPD. © 2007 Wiley‐Liss, Inc.