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

Objectives: Hematological 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. In our study, we investigate the incidence of hematological toxicities and its relation to the haplotype ATP-Binding Cassette B1 (ABCB1) which were polymorphism of C1236T, C3435T, G2677T and Glutathione S-Transferase P1 (GSTP1) A313G gene in Indonesian breast-cancer patients who receives anthracycline during chemotherapy. Methods: One hundred and thirty-eight breast-cancer patients in H. Adam Malik Hospital, Medan, Indonesia who were in the inclusion criteria were recruited in this retrospective cohort study. The DNA of patients was extracted from the peripheral leukocytes. Single nucleotide polymorphism (SNP) ABCB1 and GSTP1 were examined by the PCR-RFLP method. Data on patient characteristics and the incidence of hematological toxicity were obtained from patient medical records after three cycles of chemotherapy. Trend of absolute neutrophil count (ANC) and anemia were analyzed using the Friedmann test and the Wilcoxon signed-rank test. The Kruskal-Wallis test was performed to understand the association of ABCB1 and GSTP1 polymorphisms with the incidence of anemia and neutropenia. The frequency distribution of genotypes and alleles were determined using the Hardy-Weinberg Equilibrium (HWE). Results: A decrease of ANC was found after post chemotherapy on cycles 3 (Mean ± SD: 5644.48± 2962.545/mm3 vs 3034.89±2049.635/mm3 ), and the anemia (12.1478±1.50057 gr/dl vs 11.2746± 1.31221 gr/dl) after the patients underwent three chemotherapy cycles (p <0.05). There was no relation between ABCB1 polymorphism, either in each SNP or in the form of haplotype (the combination of more than one SNP) on the incidence of anemia and neutropenia (p> 0.05). In GSTP1 polymorphisms, no correlation between polymorphisms and anemia and neutropenia incidence (p> 0.05) was found. In our study, the ABCB1 and GSTP1 genotypes and alleles frequency distribution showed no deviation from HWE (p> 0.05). Conclusions: Patients who have performed the three cycles of hemotherapy demonstrated a susceptibility to the side effects of hematological toxicity (such as anemia and neutropenia); however, there was no relationship between ABCB1 and GSTP1 polymorphisms to hematological toxicity.

Role of Glutathione S-transferase Mu 1 and Glutathione S-transferases Theta 1 Polymorphism in the Risk of Developing Type 2 Diabetes Mellitus at Universitas Sumatera Utara Hospital, Medan

“…Several populations in the world showed that GSTM1 gene null polymorphism and/or GSTT1 had the risk of type 2 DM (T2DM) compared with healthy control group [14], [15]. GSTT1 dan GSTM1 gene polymorphism and some diseases have been studied in Indonesia [16], [17], [18], [19], however, so far not research on T2DM. Therefore, this study was aimed to determine the role of GSTM1 and GSTT1 gene polymorphism in T2DM at Universitas Sumatera Utara Hospital, Medan, Indonesia.…”