Key result
Genetic polymorphisms in ABCC2 and CBR3 were significantly associated with variations in complete response and toxicities, including a 9.5-fold increased risk of anemia with CBR3 AA in NHL.
Why the study?
To compare the effect of genes involved in doxorubicin transport (ABCC2) and metabolism (CRB3) on complete response and adverse effects in Egyptian lymphoma patients.
Do genetic polymorphisms in ABCC2 and CBR3 affect complete response and adverse effects in Egyptian lymphoma patients receiving doxorubicin?
Observational
Do genetic polymorphisms in ABCC2 and CBR3 affect complete response and adverse effects in Egyptian lymphoma patients receiving doxorubicin?
Effect estimate: 9.5-fold elevation in risk
Genetic polymorphisms in ABCC2 and CBR3 may predict interindividual variations in complete response and toxicities in lymphoma patients receiving doxorubicin.
CBR3 AA alleles may increase anemia risk with doxorubicin in NHL; hypothesis-generating for pharmacogenetic testing before prospective validation.
Aim Compare the effect of genes involved in the doxorubicin transport (ABCC2) and metabolism (CRB3) on the complete response and adverse effects in Egyptian lymphoma patients. Patients and methods Hodgkin and non-Hodgkin lymphoma (HL and NHL) patients received DOX-containing regimens for at least six cycles. The single nucleotide polymorphisms genotyping was performed by real-time PCR. Complete blood count, positron emission tomography, kidney function, and liver function tests were measured at baseline, during, and after the end of DOX cycles. Adverse effects were documented after the first cycle of therapy. Results The AA alleles of ABCC2 in HL were associated significantly with a decrease in the risk of leukopenia, while in NHL, GA was associated with a significant increase in the risk of lymphopenia. Still, the GA allele in HL patients was significantly associated with an increase in the risk of infection decreased by combining GA/AA alleles, but with NHL, the risk of infection increased with GA alleles. For the CBR3 variants in NHL, AA alleles were associated with a 9.5-fold elevation in the risk of anemia compared to GG. HL patients with AA alleles of CBR3 were associated with a significant elevation in the risk of infection, with a decrease to only three-fold elevation by combining GA/AA alleles compared to GG. Muscle pain in both diseases was significantly correlated with AA alleles. Interestingly, AA was significantly associated with an increase in the risk of muscle pain in HL patients compared to GG. The GA and AA alleles of NHL patients were associated with decreased complete response compared to GG alleles. Conclusion Genetic polymorphisms in ABCC2 and CBR3 may reveal interindividual variations to have a complete response and different toxicities.
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Abdelkawy et al. (2025) conducted an observational in Hodgkin and non-Hodgkin lymphoma. ABCC2 and CBR3 genetic polymorphisms vs. Reference alleles (e.g., GG) was evaluated on Complete response and adverse effects (9.5-fold elevation in risk). Genetic polymorphisms in ABCC2 and CBR3 were significantly associated with variations in complete response and toxicities, including a 9.5-fold increased risk of anemia with CBR3 AA in NHL.
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