The Relation of Haplotype ATP-binding Cassette B1 and Glutathione S-transferase P1 A313G Genes with Hematological Toxicity in Indonesian Breast Cancer Patients Receiving Chemotherapy.

Abstract

ObjectivesHematological toxicity induced by chemotherapy is known to be caused by multiple factors, including genetic factors such as polymorphisms. The polymorphisms may occur in drug efflux transporter proteins and enzymes involved in drug metabolism. We investigate the incidence of hematological toxicities and their relation to the haplotype ATP-binding cassette B1 (ABCB1) which were polymorphisms of C1236T, C3435T, G2677T, and glutathione S-transferase P1 (GSTP1) A313G genes in Indonesian breast cancer patients who received anthracycline during chemotherapy.MethodsThis retrospective cohort study was conducted on 138 breast cancer patients who underwent three cycles of chemotherapy in H. Adam Malik Hospital, Medan, Indonesia, who satisfied the inclusion criteria. The DNA of these patients was extracted from the peripheral leukocytes. Single nucleotide polymorphism (SNP) ABCB1 and GSTP1 were examined by the polymerase chain reaction-restriction fragment length polymorphism method. Data on patient characteristics and the incidence of hematological toxicity after each of the three cycles of chemotherapy were obtained from the medical records. The variations in absolute neutrophil count (ANC) and anemia were analyzed using the Friedmann test and the Wilcoxon signed-rank test. The Kruskal-Wallis test was used to investigate the association of ABCB1 and GSTP1 polymorphisms with anemia and neutropenia. The frequency distributions of genotypes and alleles were determined using the Hardy-Weinberg Equilibrium (HWE).ResultsPost the chemotherapy cycles, there was decrease in ANC (Mean±SD: 5 644.4±2 962.5 mm3 vs. 3 034.8±2 049.6 mm3) and increase in anemia (12.1±1.5 g/dL vs. 11.2± 1.3 g/dL) (p < 0.050 for each). No relation was observed between ABCB1 polymorphism, either in each SNP or in the form of haplotype (the combination of more than one SNP), and the incidence of anemia and neutropenia (p > 0.050). There was also no correlation between GSTP1 polymorphisms, anemia and neutropenia incidence (p > 0.050). The ABCB1 and GSTP1 genotypes and alleles frequency distribution showed no deviation from HWE (p > 0.050).ConclusionsIndonesia breast cancer patients who underwent three cycles of chemotherapy demonstrated susceptibility to hematological toxicity by developing side effects such as anemia and neutropenia. However, no relationship was found between hematological toxicity and ABCB1 and GSTP1 polymorphisms.