Association of Multi-Drug Resistance-1 (MDR1) Gene Polymorphism with Leukocytopenia in Breast Cancer Patients treated with Chemotherapy
- 10.2991/phico-16.2017.5How to use a DOI?
- MDR1 C3435T polymorphism, leukocytopenia, doxorubicin-paclitaxel, breast cancer
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.
- © 2017, the Authors. Published by Atlantis Press.
- Open Access
- This is an open access article distributed under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).
Cite this article
TY - CONF AU - Siti Syarifah AU - Tri Widyawati AU - Kamal B.Siregar AU - Yahwardiah Siregar PY - 2016/12 DA - 2016/12 TI - Association of Multi-Drug Resistance-1 (MDR1) Gene Polymorphism with Leukocytopenia in Breast Cancer Patients treated with Chemotherapy BT - Proceedings of the 1st Public Health International Conference (PHICo 2016) PB - Atlantis Press SP - 23 EP - 27 SN - 2468-5739 UR - https://doi.org/10.2991/phico-16.2017.5 DO - 10.2991/phico-16.2017.5 ID - Syarifah2016/12 ER -