TY - JOUR
T1 - A DPYD variant (y186c) specific to individuals of african descent in a patient with life-threatening 5-fu toxic effects
T2 - Potential for an individualized medicine approach
AU - Saif, Muhammad Wasif
AU - Lee, Adam M.
AU - Offer, Steven M.
AU - McConnell, Kathleen
AU - Relias, Valerie
AU - Diasio, Robert B.
N1 - Funding Information:
We thank the Mayo Clinic Medical Genome Facility for sequencing services. The Medical Genome Facility is supported, in part, by the Mayo Clinic Center for Individualized Medicine and the Mayo Clinic Cancer Center, which is supported, in part, by National Cancer Institute Cancer Center Support grant 5P30 CA15083-37 .
PY - 2014/1
Y1 - 2014/1
N2 - 5-Fluorouracil (5-FU) is commonly administered as a therapeutic agent for the treatment of various aggressive cancers. Severe toxic reactions to 5-FU have 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 variety of genetic variations in DPYD, the gene encoding DPD, are known to result in decreased DPD enzyme activity and to contribute to 5-FU toxic effects. Recently, it was reported that healthy African American individuals carrying the Y186C DPYD variant (rs115232898) had significantly reduced DPD enzyme activity compared with noncarriers of Y186C. Herein, we describe for the first time, to our knowledge, an African American patient with cancer with the Y186C variant who had severe toxic effects after administration of the standard dose of 5-FU chemotherapy. The patient lacked any additional toxic effecteassociated variations in the DPYD gene or the thymidylate synthase (TYMS) promoter. This case 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 toxic effects in individuals of African ancestry.
AB - 5-Fluorouracil (5-FU) is commonly administered as a therapeutic agent for the treatment of various aggressive cancers. Severe toxic reactions to 5-FU have 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 variety of genetic variations in DPYD, the gene encoding DPD, are known to result in decreased DPD enzyme activity and to contribute to 5-FU toxic effects. Recently, it was reported that healthy African American individuals carrying the Y186C DPYD variant (rs115232898) had significantly reduced DPD enzyme activity compared with noncarriers of Y186C. Herein, we describe for the first time, to our knowledge, an African American patient with cancer with the Y186C variant who had severe toxic effects after administration of the standard dose of 5-FU chemotherapy. The patient lacked any additional toxic effecteassociated variations in the DPYD gene or the thymidylate synthase (TYMS) promoter. This case 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 toxic effects in individuals of African ancestry.
UR - http://www.scopus.com/inward/record.url?scp=84893039495&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84893039495&partnerID=8YFLogxK
U2 - 10.1016/j.mayocp.2013.09.008
DO - 10.1016/j.mayocp.2013.09.008
M3 - Article
C2 - 24388031
AN - SCOPUS:84893039495
SN - 0025-6196
VL - 89
SP - 131
EP - 136
JO - Mayo Clinic Proceedings
JF - Mayo Clinic Proceedings
IS - 1
ER -
