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首页> 外文会议>Public Health International Conference >Association of Multi-Drug Resistance-1 (MDR1) Gene Polymorphism with Leukocytopenia in Breast Cancer Patients treated with Chemotherapy
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Association of Multi-Drug Resistance-1 (MDR1) Gene Polymorphism with Leukocytopenia in Breast Cancer Patients treated with Chemotherapy

机译：多药物抗性-1（MDR1）基因多态性与化疗治疗的乳腺癌患者白细胞减少症

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Breast cancer incidence rates tend to increase in Indonesia and worldwide. Chemotherapy is an important breast cancer treatment which improve survival rate but also has many side effects. Leukocytopenia is one of the most common side effects that can be life-threatening due to opportunistic infection. Genetic polymorphism has been linked to inter-individual variations in terms of toxicity response of anticancer drugs. C3435T polymorphism in exon 26 of Multi-Drug Resistance 1 (MDR-1) gene which encodes P-glycoprotein (P-gp) is considered to be associated with increase of leukocytopenia incidence during chemotherapy. This study aim to investigate the association between MDR1 C3435T polymorphism with the grading of leukocytopenia in breast cancer patients treated with chemotherapy. 72 Indonesian female breast cancer patients from Haji Adam Malik Hospital who received chemotherapy containing doxorubicin-paclitaxel were selected for this cohort study. DNA was extracted from peripheral leukocytes and MDR1 C3435T polymorphism was analyzed with polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Patient data were collected for 3 cycles of chemotherapy. Association between MDR1 C3435T polymorphism with the grading of leukocytopenia was assessed using Kruskal-Wallis test. Decline of absolute leucocyte count during 3 cycles of chemotherapy was assessed using Wilcoxon test. Genotype deviation and allele frequencies were also determined by Hardy-Weinberg Equilibrium. Patients were divided into 4 ethnics: Bataknese, Minangkabau, Javanese and Acehnese. Distribution of MDR1 C3435T polymorphism was varied among these ethnics. The frequencies of MDR1 C3435T genotype for wildtype (CC) was 22 (30,6%), heterozygous (CT) was 38 (52,8%) and homozygous mutant (TT) was 12 (16,7%). There was no association between MDR1 C3435T polymorphism and the grading of leukocytopenia (p>0,05). The average of absolute leukocyte count was differ after the second chemotherapy and after the third chemotherapy (p<0,05). The allele and genotype frequency from Hardy-Weinberg Equilibrium showed no significant deviation. MDR1 C3435T polymorphism had no association with leukocytopenia in breast cancer patients treated with doxorubicin-taxan regimen, meanwhile there was a trend of absolute leukocyte count declining post chemotherapy cycle 2.
机译：乳腺癌发病率倾向于增加印度尼西亚和全球。化疗是一种重要的乳腺癌治疗，可提高存活率，但也具有许多副作用。白细胞病是由于机会感染导致危及生命的最常见的副作用之一。遗传多态性与抗癌药物的毒性反应方面已与个体间变异有关。在编码p-糖蛋白（P-GP）的多药物抗性1（MDR-1）基因的外显子26中的C3435T多态性被认为是在化疗期间的白细胞缺乏发病率的增加与白细胞蛋白发病率的增加有关。本研究旨在探讨MDR1 C3435T多态性与化疗治疗乳腺癌患者白细胞缺乏症之间的关联。 72印度尼西亚雌性乳腺癌患者来自Haji Adam Malik医院的患者，他选择了含有多柔比星 - 紫杉醇的化疗，为这项队列研究。从外周白细胞中提取DNA，用聚合酶链反应限制片段长度多态性（PCR-RFLP）分析MDR1 C3435T多态性。收集患者数据3次化疗。利用Kruskal-Wallis试验评估了MDR1 C3435T多态性与白细胞减少症分级的关联。使用Wilcoxon试验评估3次化疗期间绝对白细胞计数的下降。基因型偏差和等位基因频率也由Hardy-Weinberg均衡决定。患者分为4个民族：Bataknese，Minangkabau，Javanese和Acehnese。这些族人的MDR1 C3435T多态性的分布变化。用于野生型（CC）的MDR1 C3435T基因型的频率为22（30,6％），杂合（CT）为38（52,8％），纯合突变体（TT）为12（16,7％）。 MDR1 C3435T多态性与白细胞减少症的评分之间没有关联（P> 0,05）。在第二种化疗后和第三种化疗之后，绝对白细胞计数的平均值不同（P <0.05）。来自Hardy-Weinberg均衡的等位基因和基因型频率显示出没有显着偏差。 MDR1 C3435T多态性与多柔比蛋白 - 税前治疗治疗的乳腺癌患者中的白细胞缺乏症无关，同时存在绝对白细胞计数的趋势下降后化疗周期2。

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