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Association of Multi-Drug Resistance-1 (MDR1) Gene C3435T
Polymorphism With Grading of Leucopenia In Breast Cancer Patients
treated with Chemotherapy
Siti Syarifah1, Tri Widyawati1, Kamal B.Siregar2, Yahwardiah Siregar3,4
1
Department of Pharmacology and Therapeutic, Faculty of Medicine, Universitas
Sumatera Utara
2
Department of Surgery Subdivision Oncology Surgery, Faculty of Medicine,
Universitas Sumatera Utara
3
Department of Biochemistry, Faculty of Medicine, Universitas Sumatera Utara
4
Biomedical Master Programme, Faculty of Medicine, Universitas Sumatera Utara
Correspondence: [email protected]
ABSTRACT
Background: Breast cancer incidence rates tend to increase in Indonesia and
worldwide. Chemotherapy is an important breast cancer treatment that alleviate
survival rate but also has various adverse events. Leucopenia is one of the most
common adverse events 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 MultiDrug Resistance 1 (MDR-1) gene which codes P-glycoprotein (P-gp) is
considered to be associated with an increase of leucopenia incidence during
chemotherapy.
Objective: To investigate the association between MDR1 C3435T polymorphism
with the grading of leucopenia in breast cancer patients treated with chemotherapy
Method: 72 Indonesian female breast cancer patients from Haji Adam Malik
Hospital who received chemotherapy containing doxorubicin-taxan were selected
for this cohort study. DNA was extracted from peripheral leucocytes 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 leucopenia 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
Result: Patients were divided into 4 ethnics: Bataknese, Padangnese, Javanese
and Acehnese. Distribution of MDR1 C3435T polymorphism varies 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 leucopenia (p>0,05). The average of absolute leucocyte count was
differ after the first chemotherapy and after the third chemotherapy (p<0,05). The
allele and genotype frequency from Hardy-Weinberg Equilibrium showed no
significant deviation.
Conclusion: MDR1 C3435T polymorphism had no association with the grading
of leucopenia in breast cancer patients treated with doxorubicin-taxan regimen,
meanwhile there was a trend of absolute leucocyte count declining during the 3
cycles of chemotherapy.
Keywords: MDR1 C3435T polymorphism; leucopenia; doxorubicin-taxan; breast
cancer