A DPYD variant (Y186C) specific to individuals of African descent in a patient with life-threatening 5-FU toxicity: potential for an individualized medicine approach

M. Wasif Saif; Adam M. Lee; Steven M. Offer; Kathleen McConnell; Valerie Relias; Robert B. Diasio

doi:10.1016/j.mayocp.2013.09.008

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A DPYD variant (Y186C) specific to individuals of African descent in a patient with life-threatening 5-FU toxicity: potential for an individualized medicine approach

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A DPYD variant (Y186C) specific to individuals of African descent in a patient with life-threatening 5-FU toxicity: potential for an individualized medicine approach

M. Wasif Saif, Adam M. Lee, Steven M. Offer, Kathleen McConnell, Valerie Relias and Robert B. Diasio

Mayo Clinic proceedings, Vol.89(1), pp.131-136

01/01/2014

DOI: 10.1016/j.mayocp.2013.09.008

PMCID: PMC4071869

PMID: 24388031

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Abstract

5-Fluorouracil (5-FU) is commonly administered as a therapeutic agent for the treatment of various aggressive cancers. Severe toxicity to 5-FU has been associated with decreased levels of dihydropyrimidine dehydrogenase (DPD) enzyme activity. Manifestations of 5-FU toxicity typically include cytopenia, diarrhea, stomatitis, mucositis, neurotoxicity, and, in extreme cases, death. A number of genetic variations within DPYD , the gene encoding DPD, are known to result in decreased DPD enzyme activity and contribute to 5-FU toxicity. Recently it was shown that healthy African American individuals carrying the Y186C DPYD variant (rs115232898) had significantly reduced DPD enzyme activity compared to non-carriers of Y186C. In the present study, we describe for the first time an African American cancer patient with the Y186C variant who developed severe toxicity following administration of the standard dose of 5-FU chemotherapy. The patient lacked any additional toxicity associated variations within the DPYD gene or the thymidylate synthase ( TYMS ) promoter. This case report suggests that Y186C may have contributed to 5-FU toxicity in this patient and supports the use of Y186C as a predictive marker for 5-FU toxicity in individuals of African ancestry.

Details

Title: Subtitle: A DPYD variant (Y186C) specific to individuals of African descent in a patient with life-threatening 5-FU toxicity: potential for an individualized medicine approach
Creators: M. Wasif Saif - Tufts Medical Center
Adam M. Lee - Mayo Clinic
Steven M. Offer - Mayo Clinic
Kathleen McConnell - Tufts Medical Center
Valerie Relias - Tufts Medical Center
Robert B. Diasio - Mayo Clinic
Resource Type: Journal article
Publication Details: Mayo Clinic proceedings, Vol.89(1), pp.131-136
DOI: 10.1016/j.mayocp.2013.09.008
PMID: 24388031
PMCID: PMC4071869
ISSN: 0025-6196
eISSN: 1942-5546
Language: English
Date published: 01/01/2014
Academic Unit: Pathology
Record Identifier: 9984618643202771

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