Search tips
Search criteria 


Logo of brjcancerBJC HomepageBJC Advance online publicationBJC Current IssueSubmitting an article to BJCWeb feeds
Br J Cancer. 1997; 75(2): 178–179.
PMCID: PMC2063286

Mutations at codon 974 of the DPYD gene are a rare event.


A mutation at codon 974 of the dihydropyrimidine dehydrogenase (DPD) gene was previously described in a cancer patient with undetectable DPD enzyme activity who experienced severe toxicity when treated with 5-fluorouracil. We have studied the frequency of this mutation in 29 Scottish subjects with low DPD enzyme activity and in 274 American subjects. We detected no mutations in the 606 alleles studied and conclude that mutations at codon 974 are a rare event.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (437K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Etienne MC, Lagrange JL, Dassonville O, Fleming R, Thyss A, Renée N, Schneider M, Demard F, Milano G. Population study of dihydropyrimidine dehydrogenase in cancer patients. J Clin Oncol. 1994 Nov;12(11):2248–2253. [PubMed]
  • Gonzalez FJ, Fernandez-Salguero P. Diagnostic analysis, clinical importance and molecular basis of dihydropyrimidine dehydrogenase deficiency. Trends Pharmacol Sci. 1995 Oct;16(10):325–327. [PubMed]
  • Harris BE, Carpenter JT, Diasio RB. Severe 5-fluorouracil toxicity secondary to dihydropyrimidine dehydrogenase deficiency. A potentially more common pharmacogenetic syndrome. Cancer. 1991 Aug 1;68(3):499–501. [PubMed]
  • Houyau P, Gay C, Chatelut E, Canal P, Roché H, Milano G. Severe fluorouracil toxicity in a patient with dihydropyrimidine dehydrogenase deficiency. J Natl Cancer Inst. 1993 Oct 6;85(19):1602–1603. [PubMed]
  • Lu Z, Zhang R, Diasio RB. Dihydropyrimidine dehydrogenase activity in human peripheral blood mononuclear cells and liver: population characteristics, newly identified deficient patients, and clinical implication in 5-fluorouracil chemotherapy. Cancer Res. 1993 Nov 15;53(22):5433–5438. [PubMed]
  • McLeod HL, Lin JS, Scott EP, Pui CH, Evans WE. Thiopurine methyltransferase activity in American white subjects and black subjects. Clin Pharmacol Ther. 1994 Jan;55(1):15–20. [PubMed]
  • McMurrough J, McLeod HL. Analysis of the dihydropyrimidine dehydrogenase polymorphism in a British population. Br J Clin Pharmacol. 1996 May;41(5):425–427. [PMC free article] [PubMed]
  • Meinsma R, Fernandez-Salguero P, Van Kuilenburg AB, Van Gennip AH, Gonzalez FJ. Human polymorphism in drug metabolism: mutation in the dihydropyrimidine dehydrogenase gene results in exon skipping and thymine uracilurea. DNA Cell Biol. 1995 Jan;14(1):1–6. [PubMed]
  • Milano G, Etienne MC. Potential importance of dihydropyrimidine dehydrogenase (DPD) in cancer chemotherapy. Pharmacogenetics. 1994 Dec;4(6):301–306. [PubMed]
  • Naguib FN, el Kouni MH, Cha S. Enzymes of uracil catabolism in normal and neoplastic human tissues. Cancer Res. 1985 Nov;45(11 Pt 1):5405–5412. [PubMed]
  • Takimoto CH, Lu ZH, Zhang R, Liang MD, Larson LV, Cantilena LR, Jr, Grem JL, Allegra CJ, Diasio RB, Chu E. Severe neurotoxicity following 5-fluorouracil-based chemotherapy in a patient with dihydropyrimidine dehydrogenase deficiency. Clin Cancer Res. 1996 Mar;2(3):477–481. [PubMed]
  • Wei X, McLeod HL, McMurrough J, Gonzalez FJ, Fernandez-Salguero P. Molecular basis of the human dihydropyrimidine dehydrogenase deficiency and 5-fluorouracil toxicity. J Clin Invest. 1996 Aug 1;98(3):610–615. [PMC free article] [PubMed]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK