title: 5-Fluorouracil toxicity-attributable IVS14 + 1G > A mutation of the dihydropyrimidine dehydrogenase gene in Polish colorectal cancer patients.
abstract: DPYD gene encodes dihydropyrimidine dehydrogenase which is the initial and rate-limiting enzyme in the metabolism of 5-fluorouracil (5-FU). The aim of our study was PCR-RFLP based-genetic testing for the most common 5-FU toxicity-attributable IVS14 + 1G > A DPYD mutation (DPYD(*)2A) in 252 Polish colorectal cancer (CRC) patients treated with this adjuvant chemotherapeutic regimen after surgery. The DPYD(*)2A allele was identified only in one patient: a male who was one of 4 CRC patients suffering from grades 3-4 myelotoxicity upon 5-FU chemotherapy. We conclude that IVS14 + 1G > A DPYD (DPYD(*)2A) variant occurs in the Polish population and is responsible for a significant proportion of life-threatening toxicity of 5-FU.
authors.affiliation: Department of Oncological Surgery, Pomeranian Medical University, Powstańców Wlkp. 72, PL 70-111 Szczecin, Poznań, Poland.
authors.forename: Violetta
authors.initials: V
authors.lastname: Sulzyc-Bielicka
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Bińczak-Kuleta
authors.forename: Wiesława
authors.initials: W
authors.lastname: Pioch
authors.forename: Józef
authors.initials: J
authors.lastname: Kładny
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Gziut
authors.forename: Dariusz
authors.initials: D
authors.lastname: Bielicki
authors.forename: Andrzej
authors.initials: A
authors.lastname: Ciechanowicz
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects* / Q000627:therapeutic use; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology*; D011044:Poland / Q000453:epidemiology; D012150:Polymorphism, Restriction Fragment Length; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000964:Antimetabolites, Antineoplastic; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil