Influence of polymorphisms in anthracyclines metabolism genes in the standard induction chemotherapy of acute myeloid leukemia

Abstract

Objectives Genetic variability in anthracycline metabolism could modify the response and safety of acute myeloid leukemia (AML) induction. MethodsPolymorphisms in genes that encodes enzymes of anthracyclines metabolic pathway (CBR3: rs1056892, rs8133052, NQO1: rs1800566, NQO2: rs1143684, NOS3: rs1799983, rs2070744) were evaluated in 225 adult de novo AML patients. ResultsThe variant CBR3 rs8133052 was associated with lower hepatotoxicity (P = 0.028). Wild-type genotype of NQO2 rs1143684 was related to higher complete remission (P = 0.014), and the variant allele with greater gastrointestinal toxicity (P = 0.024). However, the variant genotype of NQO1 rs1800566 was associated with mucositis (P = 0.018), but heterozygous genotype showed less gastrointestinal toxicity (P = 0.028) and thrombocytopenia (P = 0.009). Protective effects against nephrotoxicity and thrombocytopenia were reported with variant NOS3 rs1799983 (P = 0.006, P = 0.014), whereas carriers of NOS3 rs2070744 showed higher hepatotoxicity and thrombocytopenia (P = 0.017, P = 0.013). ConclusionsThis study supports the influence of genetic variability of idarubicin metabolizing could be critical in predicting anthracycline-induced toxicities.

Association of Gene Polymorphisms with Breast Cancer Risk in the Kazakh Population

“…The T/T rs1143684 variant was more frequently encountered in cases of diagnosed adenocarcinoma of luminal type B, i.e., hormone positive; the C/C rs1143684 genotype was typical for patients with Her2neu-positive tumors, which implies the use of targeted drugs for Her2neu receptors. The dependence of histological and phenotypic breast tumor profiles on patient genotype has been investigated in different populations and continues to be studied (Mahdavi et al, 2019;Megías-Vericat et al, 2021;Sirisena et al, 2018;Wendt and Margolin, 2019). It was investigated (Alimardani et al, 2021) that the G allele rs799917 and the G allele rs1713611 were statistically significantly associated with the age of patients (range 50-59 years) diagnosed first with breast cancer in the Sri Lankan population.…”

Impact of single-nucleotide variants and nutritional status on population pharmacokinetics of Doxorubicin, and its effect on cardiotoxicity in children with leukemia

“…One of the genetic aspects mainly associated with PopPK modification of a drug are those associated with extracellular transporters. 15,16 The ABCC1 gene encodes for an extracellular drug transporter, the rs3743527 SNV in this gene has been associated with protection against cardiotoxicity by DOX, possibly due to the action of the pharmacokinetic modification of DOX. 17 As mentioned above, poor protein–calorie nutrition is associated with decreased response to chemotherapy, 18 for this reason, the study of the influence of nutritional status as a covariate associated with the PopPK variation of DOX is a very important aspect that should be considered.…”