Genetic polymorphisms of ABCC2 and CBR3 can influence the efficacy and toxicity of doxorubicin therapy in Egyptian patients with non-Hodgkin lymphoma.

This study investigated the impact of single nucleotide polymorphisms (SNPs) in genes involved in doxorubicin (DOX) transport and metabolism on clinical outcomes and toxicity in Egyptian patients with non-Hodgkin lymphoma. Ninety-two patients received at least six DOX treatment cycles. SNP genotyping was performed using real-time PCR with high-resolution melting analysis. Laboratory tests were conducted at baseline, during, and after treatment. The AA genotype of ABCC2 (rs8187710) showed the strongest association with elevated DOX plasma levels and a significantly increased risk of acute cardiotoxicity (OR 26.9; 95% CI: 1.47-492; p = 0.026). The GA genotype was linked to a lower complete response rate and increased risks of leukopoenia (OR 2.66; 95% CI: 1.07-6.61; p = 0.034) and lymphocytopenia (OR 10; 95% CI: 3.57-27.9; p < 0.0001), with intermediate peak DOX levels. For CBR3 (rs8133052), the GA genotype was significantly associated with a higher risk of anaemia (OR 3.5; 95% CI: 1.05-11.7; p = 0.042), acute cardiotoxicity (OR 4.4; 95% CI: 1.86-11.5; p = 0.002), cardiac-related symptoms, and higher peak plasma DOX levels, along with reduced complete response. Polymorphisms in ABCC2 and CBR3 genes may contribute to individual variability in DOX-related toxicity and treatment response.