DPYD c.1905 + 1G>A Promotes Fluoropyrimidine-Induced Anemia, a Prognostic Factor in Disease-Free Survival, in Colorectal Cancer

Genet Test Mol Biomarkers. 2021 Apr;25(4):276-283. doi: 10.1089/gtmb.2020.0285.

Abstract

Background and Aim: In 10-30% of colorectal cancer (CRC) patients, toxic reactions occur after fluoropyrimidine-based chemotherapy. A dihydropyridine dehydrogenase (DPYD) gene variant, c.1905 + 1G>A, leads to intolerance to fluoropyrimidines. Due to the low frequency of this variant in many populations, the prevalence of fluoropyrimidine-induced hematologic side effects in CRC patients with the c.1905 + 1G>A variant is unclear. In this study, we investigated the prevalence of the DPYD c.1905 + 1 variants in a Turkish CRC cohort and the potential effects of these variants on fluoropyrimidine-induced hematologic side effects. Materials and Methods: The DPYD c.1905 + 1 variant was genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis and confirmed by Sanger sequencing in peripheral blood samples of 100 CRC patients who received fluoropyrimidine-based chemotherapy and 60 healthy volunteers. The association of c.1905 + 1 variants with susceptibility to hematologic side effects was evaluated. Results: The DPYD c.1905 + 1G>A variant was more common in the CRC group than in the healthy control group (p = 0.001). The presence of the c.1905 + 1G>A variant was associated with thrombocytopenia (p = 0.039) and anemia (p = 0.035). CRC patients with fluoropyrimidine-induced anemia had shorter disease-free survival than CRC patients without fluoropyrimidine-induced anemia (p = 0.0009). Conclusions: Before administering fluoropyrimidine-based chemotherapy, genetic screening for the DPYD c.1905 + 1G>A variant should be performed with the aim of preventing anemia and anemia-induced complications in CRC patients.

Keywords: DPYD c.1905 + 1G>A; anemia; colorectal cancer; fluoropyrimidine.

MeSH terms

  • Adult
  • Aged
  • Anemia / chemically induced
  • Anemia / drug therapy
  • Anemia / genetics*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Pharmacological / blood
  • Biomarkers, Tumor / genetics
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / mortality
  • Dihydropyridines / pharmacology
  • Dihydrouracil Dehydrogenase (NADP) / genetics*
  • Dihydrouracil Dehydrogenase (NADP) / metabolism
  • Disease-Free Survival
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Oxidoreductases / genetics
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Turkey / epidemiology

Substances

  • Biomarkers, Pharmacological
  • Biomarkers, Tumor
  • Dihydropyridines
  • Oxidoreductases
  • Dihydrouracil Dehydrogenase (NADP)
  • Fluorouracil