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Three different polymorphisms of the DPYD gene associated with severe toxicity following administration of 5-FU:
Deborah Mukherji1, Sarah Abdel Massih1, Arafat Tfayli1
1Division of Hematology-Oncology, Department of Internal Medicine, American University of Beirut, Beirut, Lebanon.
Background:
Dihydropyrimidine dehydrogenase deficiency secondary to polymorphisms in the DPYD gene can lead to significant toxicity associated with the administration of fluoropyrimidine chemotherapy.
Case Presentation:
We report a case of a 59-year-old Lebanese woman with metastatic pancreatic cancer who received FOLFIRINOX therapy and developed severe 5-fluorouracil toxicity after a single cycle. The entire DPYD gene was sequenced, and the patient was found to be heterozygous for three different polymorphisms that have reportedly been associated with dihydropyrimidine dehydrogenase deficiency.
Conclusion:
Because data regarding the prevalence and clinical significance of several heterozygous polymorphisms in a single DPYD gene are very limited, we suggest that full gene sequencing should be carried out, at least in populations in which the allele frequencies are unknown.
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