TY - JOUR
T1 - Dihydropyrimidine dehydrogenase deficiency in patients with severe toxicity after 5-fluorouracil
T2 - A retrospective single-center study
AU - Detailleur, Stephanie
AU - Segelov, Eva
AU - Re, Marzia Del
AU - Prenen, Hans
PY - 2021
Y1 - 2021
N2 - Background 5-Fluorouracil (5-FU) is an agent frequently used in the treatment of solid cancers. A deficiency in the enzyme that catabolizes 5-FU leads to severe toxicity. The gene responsible for this enzyme is DPYD, located on chromosome 1q22. The most prevalent alteration described is DPYD*2A, which leads to a splicing defect and thus skipping of the translation of an entire exon. The objectives of this retrospective study were to describe the frequencies of DPYD gene mutations in a Belgian population and to correlate them with the grade of toxicity. Methods This was a retrospective, single-center study conducted at the University Hospitals Leuven, by reviewing a database of patients screened for DPYD gene mutations between May 2009 and June 2015 after prolonged grade 3-4 toxicity. Polymerase chain reaction sequencing of exons 2, 6, 10, 11, 13, 18, 19 and 22, and pyrosequencing of exon 14 were performed by an in-house laboratory. Results Of the 80 patients screened, 65 were heterozygous or compound heterozygous for DPYD and 3 had a homozygous mutation. The most prevalent mutation in our population was DPYD*9A. Conclusions Despite previous reports, in our small retrospective study the most prevalent variation in patients with severe adverse events was DPYD*9A. As this variant has previously been reported to be benign, we suggest that screening for dihydropyrimidine dehydrogenase deficiency should be extended across multiple exons of the DPYD gene.
AB - Background 5-Fluorouracil (5-FU) is an agent frequently used in the treatment of solid cancers. A deficiency in the enzyme that catabolizes 5-FU leads to severe toxicity. The gene responsible for this enzyme is DPYD, located on chromosome 1q22. The most prevalent alteration described is DPYD*2A, which leads to a splicing defect and thus skipping of the translation of an entire exon. The objectives of this retrospective study were to describe the frequencies of DPYD gene mutations in a Belgian population and to correlate them with the grade of toxicity. Methods This was a retrospective, single-center study conducted at the University Hospitals Leuven, by reviewing a database of patients screened for DPYD gene mutations between May 2009 and June 2015 after prolonged grade 3-4 toxicity. Polymerase chain reaction sequencing of exons 2, 6, 10, 11, 13, 18, 19 and 22, and pyrosequencing of exon 14 were performed by an in-house laboratory. Results Of the 80 patients screened, 65 were heterozygous or compound heterozygous for DPYD and 3 had a homozygous mutation. The most prevalent mutation in our population was DPYD*9A. Conclusions Despite previous reports, in our small retrospective study the most prevalent variation in patients with severe adverse events was DPYD*9A. As this variant has previously been reported to be benign, we suggest that screening for dihydropyrimidine dehydrogenase deficiency should be extended across multiple exons of the DPYD gene.
KW - 5-fluorouracil
KW - Deficiency
KW - Dihydropyrimidine dehydrogenase
KW - Toxicity
UR - http://www.scopus.com/inward/record.url?scp=85099640376&partnerID=8YFLogxK
U2 - 10.20524/aog.2020.0551
DO - 10.20524/aog.2020.0551
M3 - Article
C2 - 33414624
AN - SCOPUS:85099640376
SN - 1108-7471
VL - 34
SP - 68
EP - 72
JO - Annals of Gastroenterology
JF - Annals of Gastroenterology
IS - 1
ER -