Association of ATP-binding cassette sub-family B member 1 gene C3435T polymorphism with neutropenia in breast cancer patients treated with chemotherapy

Latar belakang: Neutropenia merupakan salah satu efek samping dari pengobatan kemoterapi kanker payudara yang sering dijumpai. Kejadian neutropenia ini menyebabkan pasien berisiko untuk terkena infeksi dan mengakibatkan penundaan kemoterapi. Tujuan dari penelitian ini adalah mencari hubungan polimorfisme ATP-binding cassette sub-family B member 1 (ABCB1) C3435T dengan derajat neutropenia pada pasien kanker payudara yang diterapi dengan regimen yang mengandung doksorubisin-taksan. Metode: 72 perempuan Indonesia yang didiagnosis kanker payudara dan mendapat kemoterapi mengandung regimen doksorubisin-paklitaksel di Rumah Sakit Umum Pusat Haji Adam Malik Medan diikutsertakan pada penelitian kohort ini. DNA sampel diekstraksi dari leukosit perifer dan pemeriksaan polimorfisme ABCB1 C3435T dianalisis dengan metode PCRRFLP. Data karakteristik pasien dan neutropenia dilihat dari data rekam medis. Data pasien diambil selama 3 siklus kemoterapi. Uji Kruskal Wallis digunakan untuk menganalisis hubungan polimorfisme ABCB1 C3435T dengan derajat neutropenia pasca-siklus kemoterapi I-III. Uji Wilcoxon digunakan untuk menganalisis kecenderungan penurunan jumlah neutrofil absolut selama 3 siklus kemoterapi. Distribusi frekuensi genotipe dan alel ditentukan dengan Hardy-Weinberg Equilibrium. Hasil: Proporsi ABCB1 C3435T wildtype (CC) sebesar 22 (30,6%), heterozigot varian sebesar 38 (52,8%) dan homozigot varian sebesar 12 (16,7%). Tidak ditemukan hubungan polimorfisme ABCB1 C3435T dengan derajat neutropenia (p>0,05). Terdapat perbedaan rerata jumlah neutrofil absolut antara periode setelah kemoterapi I, dan III (p<0,05), tidak ada penyimpangan frekuensi genotipe dan alel yang signifikan terhadap Hardy-Weinberg Equilibrium. Kesimpulan: Polimorfisme ABCB1 C3435T tidak berhubungan dengan derajat neutropenia pada pasien kanker payudara yang mendapat kemoterapi mengandung doksorubisin-paklitaksel namun dijumpai kecenderungan penurunan jumlah neutrofil absolut selama pemberian 3 siklus kemoterapi. Background: 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 subfamily 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.