Association of ATP-binding cassette sub-family B member 1 gene C3435T polymorphism with neutropenia in breast cancer patients treated with chemotherapy
Abstract: Neutropenia is the
most common adverse event of breast cancer chemotherapy which can be life
threatening due to opportunistic infection, neutropenic episodes may lead to
delay or reduction of drug doses which may compromise treatment outcomes. In
this study, we investigated the association of ATP-binding cassette sub-family
B member 1 (ABCB1) gene C3435T polymorphism with the grading of neutropenia in
breast cancer patients who treated with doxorubicin-taxan.
Methods: 72 Indonesian female breast cancer patients from Haji Adam Malik
Hospital who had been diagnosed and treated with doxorubicin-taxane regimen
were selected for this cohort study. DNA was extracted from peripheral
leucocytes and ABCB1 C3435T polymorphism was analyzed with PCR-RFLP. Patient
data were collected from patient’s medical record for 3 cycles of chemotherapy.
Association between ABCB1 C3435T polymorphism with neutropenia was assessed
using Kruskal-Wallis test. Decline of absolute neutrophil count was assessed
using Wilcoxon test. Genotype deviation and allele frequencies were also
determined by Hardy-Weinberg Equilibrium.
Results: The frequencies of ABCB1 C3435T genotype for wildtype (CC),
heterozygous (CT) and homozygous mutant (TT) was 22 (30.6%), 38 (52.8%) and 12
(16.7%) respectively. No association were found between ABCB1 C3435T
polymorphism and the grading of neutropenia (p>0.05). There was a difference
on the average of absolute neutrophil count after the first chemotherapy and
after the third chemotherapy (p<0.05). There was no significant deviation of
allele and genotype frequency from Hardy-Weinberg Equilibrium.
Conclusion: ABCB1 C3435T polymorphism had no association with the grading
of neutropenia in breast cancer patients treated with doxorubicin-taxane
regimen, however there was a trend of absolute neutrophil count declining
during the 3 cycles of chemotherapy.
Author: Siti Syarifah, Kamal
B. Siregar, Yahwardiah Siregar
Journal Code: jpkedokterangg160145