| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Clinical Trials |
Emma Children’s Hospital and Department of Clinical Chemistry, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam [A. B. P. v. K., J. H., R. M., L. Z., H. R. W., F. B., D. J. R., A. H. v. G.], and Slingeland ziekenhuis, 7009 BL Doetinchem [E. W. M.], the Netherlands
Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-fluorouracil (5FU), and it is suggested that patients with a partial deficiency of this enzyme are at risk from developing a severe 5FU-associated toxicity. In this study, we demonstrated that a lethal toxicity after a treatment with 5FU was attributable to a complete deficiency of DPD. Analysis of the DPD gene for the presence of mutations showed that the patient was homozygous for a G
A mutation in the invariant GT splice donor site flanking exon 14 (IVS14+1G>A). As a consequence, no significant residual activity of DPD was detected in peripheral blood mononuclear cells. To determine the frequency of the IVS14+1G>A mutation in the Dutch population, we developed a novel PCR-based method allowing the rapid analysis of the IVS14+1G>A mutation by RFLP. Screening for the presence of this mutation in 1357 Caucasians showed an allele frequency of 0.91%. In our view, the apparently high prevalence of the IVS14+1G>A mutation in the normal population, with 1.8% heterozygotes, warrants genetic screening for the presence of this mutation in cancer patients before the administration of 5FU.
This article has been cited by other articles:
|
|
 |
|
  S. Oie, M. Ono, H. Fukushima, F. Hosoi, H. Yano, Y. Maruyama, M. Kojiro, T. Terada, K. Hirano, M. Kuwano, et al. Alteration of dihydropyrimidine dehydrogenase expression by IFN-{alpha} affects the antiproliferative effects of 5-fluorouracil in human hepatocellular carcinoma cells Mol. Cancer Ther., August 1, 2007; 6(8): 2310 - 2318. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Grabinski Pharmacogenomics of Anticancer Agents: Implications for Clinical Pharmacy Practice Journal of Pharmacy Practice, June 1, 2007; 20(3): 246 - 251. [Abstract] [PDF]
|
|
|
|
|
|
A. Morel, M. Boisdron-Celle, L. Fey, P. Soulie, M. C. Craipeau, S. Traore, and E. Gamelin Clinical relevance of different dihydropyrimidine dehydrogenase gene single nucleotide polymorphisms on 5-fluorouracil tolerance. Mol. Cancer Ther., November 1, 2006; 5(11): 2895 - 2904. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Largillier, M.-C. Etienne-Grimaldi, J.-L. Formento, J. Ciccolini, J.-F. Nebbia, A. Ginot, M. Francoual, N. Renee, J.-M. Ferrero, C. Foa, et al. Pharmacogenetics of capecitabine in advanced breast cancer patients. Clin. Cancer Res., September 15, 2006; 12(18): 5496 - 5502. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Gardiner and E. J. Begg Pharmacogenetics, Drug-Metabolizing Enzymes, and Clinical Practice Pharmacol. Rev., September 1, 2006; 58(3): 521 - 590. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. H. Ezzeldin, A. M. Lee, L. K. Mattison, and R. B. Diasio Methylation of the DPYD Promoter: An Alternative Mechanism for Dihydropyrimidine Dehydrogenase Deficiency in Cancer Patients Clin. Cancer Res., December 15, 2005; 11(24): 8699 - 8705. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Steiner, M Seule, B Steiner, I Bauer, M Freund, C H Kohne, and P Schuff-Werner 5-Fluorouracil/irinotecan induced lethal toxicity as a result of a combined pharmacogenetic syndrome: report of a case J. Clin. Pathol., May 1, 2005; 58(5): 553 - 555. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. H. Park, B.-Y. Ryoo, H. J. Lee, S. A. Kim, and J.-H. Chung High incidence of severe hand-foot syndrome during capecitabine-docetaxel combination chemotherapy Ann. Onc., November 1, 2003; 14(11): 1691 - 1692. [Full Text] [PDF]
|
|
|
|
|
|
A. B. P. van Kuilenburg, R. Meinsma, B. A. Zonnenberg, L. Zoetekouw, F. Baas, K. Matsuda, N. Tamaki, and A. H. van Gennip Dihydropyrimidinase Deficiency and Severe 5-Fluorouracil Toxicity Clin. Cancer Res., October 1, 2003; 9(12): 4363 - 4367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. P. van Kuilenburg, J. W. Baars, R. Meinsma, and A. H. van Gennip Lethal 5-fluorouracil toxicity associated with a novel mutation in the dihydropyrimidine dehydrogenase gene Ann. Onc., February 1, 2003; 14(2): 341 - 342. [Full Text] [PDF]
|
|
|
|
|
|
C. Carnaghi, L. Rimassa, I. Garassino, P. A. Zucali, G. Masci, M. Fallini, E. Morenghi, and A. Santoro Irinotecan and raltitrexed: an active combination in advanced colorectal cancer Ann. Onc., September 1, 2002; 13(9): 1424 - 1429. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Chabner Cytotoxic Agents in the Era of Molecular Targets and Genomics Oncologist, August 1, 2002; 7(90003): 34 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Innocenti and M. J. Ratain Correspondence re: Raida, M. et al., Prevalence of a Common Point Mutation in the Dihydropyrimidine Dehydrogenase (DPD) Gene within the 5'-Splice Donor Site of Intron 14 in Patients with Severe 5-Fluorouracil (5-FU)-related Toxicity Compared with Controls. Clin. Cancer Res., 7: 2832-2839, 2001. Clin. Cancer Res., May 1, 2002; 8(5): 1314 - 1316. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
