Syarifah Siti, Widyawati Tri, Hasni Dita, Sari Mutiara Indah, Rusdiana Rusdiana, Hamdi Tasrif
Department of Pharmacology and Therapeutic, Medical Faculty, Universitas Sumatera Utara, Medan, Indonesia.
Department of Pharmacology, Medical Faculty, Universitas Baiturrahmah, Padang, Indonesia.
Oman Med J. 2022 Mar 22;37(2):e357. doi: 10.5001/omj.2022.36. eCollection 2022 Mar.
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. We investigate the incidence of hematological toxicities and their relation to the haplotype ATP-binding cassette B1 (ABCB1) which were polymorphisms of , , and glutathione S-transferase P1 () genes in Indonesian breast cancer patients who received anthracycline during chemotherapy.
This 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).
Post the chemotherapy cycles, there was decrease in ANC (Mean±SD: 5 644.4±2 962.5 mm vs. 3 034.8±2 049.6 mm) and increase in anemia (12.1±1.5 g/dL vs. 11.2± 1.3 g/dL) ( < 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 ( 0.050). There was also no correlation between GSTP1 polymorphisms, anemia and neutropenia incidence ( 0.050). The ABCB1 and GSTP1 genotypes and alleles frequency distribution showed no deviation from HWE ( 0.050).
Indonesia 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.
已知化疗引起的血液学毒性是由多种因素导致的，包括基因多态性等遗传因素。这些多态性可能发生在药物外排转运蛋白和参与药物代谢的酶中。我们调查了接受蒽环类药物化疗的印度尼西亚乳腺癌患者血液学毒性的发生率及其与单倍型三磷酸腺苷结合盒转运体B1（ABCB1）以及谷胱甘肽S - 转移酶P1（GSTP1）基因多态性的关系。
这项回顾性队列研究在印度尼西亚棉兰市H. Adam Malik医院对138例符合纳入标准且接受了三个周期化疗的乳腺癌患者进行。从这些患者的外周血白细胞中提取DNA。采用聚合酶链反应 - 限制性片段长度多态性方法检测单核苷酸多态性（SNP）ABCB1和GSTP1。从病历中获取患者特征数据以及三个化疗周期中每个周期后血液学毒性的发生率。使用Friedmann检验和Wilcoxon符号秩检验分析绝对中性粒细胞计数（ANC）和贫血的变化。使用Kruskal - Wallis检验研究ABCB1和GSTP1多态性与贫血和中性粒细胞减少的相关性。使用哈迪 - 温伯格平衡（HWE）确定基因型和等位基因的频率分布。
化疗周期后，ANC下降（均值±标准差：5644.4±2962.5/mm³ 对 3034.8±2049.6/mm³），贫血增加（12.1±1.5 g/dL对11.2±1.3 g/dL）（每项P < 0.050）。在每个SNP或单倍型形式（多个SNP的组合）的ABCB1多态性与贫血和中性粒细胞减少的发生率之间未观察到相关性（P > 0.050）。GSTP1多态性与贫血和中性粒细胞减少发生率之间也无相关性（P > 0.050）。ABCB1和GSTP1基因型和等位基因频率分布未偏离HWE（P > 0.050）。
接受三个周期化疗的印度尼西亚乳腺癌患者通过出现贫血和中性粒细胞减少等副作用表现出对血液学毒性的易感性。然而，未发现血液学毒性与ABCB1和GSTP1多态性之间存在关联。
