The SLC22A2 gene is a determinant of hematological toxicity of oxaliplatin in patients with colorectal cancer

Int J Clin Pharmacol Ther. 2023 Jan;61(1):1-7. doi: 10.5414/CP204156.

Abstract

Objective: To investigate the association between polymorphisms in the SLC22A2 gene and the hematological toxicity of oxaliplatin in colorectal cancer (CRC) patients receiving chemotherapy.

Materials and methods: A total of 81 patients with colon or rectal cancer were included in the study. The single nucleotide polymorphisms (SNPs) rs3127573, rs316019, and rs1869641 of the SLC22A2 gene were selected for genotyping using the polymerase chain reaction (PCR) and sequence analysis. Oxaliplatin-associated hematological toxicities were evaluated using the Common Toxicity Criteria for Adverse Events (CTCAE, Version 5.0).

Results: The rs1869641 genotype was significantly associated with the occurrence of thrombocytopenia (p = 0.047), whereas the rs316019 genotype was significantly associated with severity of leucopenia and neutropenia (p = 0.004 and 0.001, respectively). The rs3127573 genotype was not associated with hematological toxicities arising during chemotherapy with oxaliplatin.

Conclusion: It is shown here, for the first time, that the rs316019 gene variant of the SLC22A2 gene may be associated with the hematological toxicity of oxaliplatin. Patients with genotype CA/AA of rs316019 are more likely to develop serious hematological adverse effects.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • Fluorouracil / therapeutic use
  • Genotype
  • Humans
  • Neutropenia* / chemically induced
  • Organic Cation Transporter 2 / genetics
  • Organic Cation Transporter 2 / therapeutic use
  • Oxaliplatin / adverse effects
  • Polymorphism, Single Nucleotide

Substances

  • Oxaliplatin
  • Fluorouracil
  • SLC22A2 protein, human
  • Organic Cation Transporter 2