Hubungan Polimorfisme Gen Reseptor Vitamin D Fok-1 (rs2228570) dan Kadar Vitamin D Plasma Terhadap Proliferasi Sel (Ki-67) pada Kanker Payudara

Abstract

Pendahuluan: Kanker payudara merupakan salah satu masalah kesehatan serius pada wanita. Dalam aktivitasnya reseptor vitamin D bersama ligannya vitamin D berperan di dalam kanker payudara. Fok-1 merupakan salah satu polimorfisme reseptor vitamin D pada area start codon di exon 2, yaitu adanya konversi basa (C>T) sehingga menghasilkan produk protein dengan panjang yang berbeda. Perubahan pada reseptor vitamin D dapat menyebabkan perubahan sinyal seluler oleh vitamin D yang dapat mempengaruhi progresivitas dari sel tumor yang dinilai berdasarkan proliferasi sel Ki-67 pada kanker payudara Tujuan: untuk mengetahui hubungan polimorfisme gen reseptor vitamin D Fok-1(rs2228570) dan kadar vitamin D plasma terhadap proliferasi sel (Ki-67) pada kanker payudara Metode: sampel darah diambil dari 50 orang pasien kanker payudara kasus baru dan belum pernah menjalani kemoterapi sejak Oktober 2017 hingga Februari 2018 di RSUP H. Adam Malik Medan. Isolasi DNA dan amplifikasi gen diperiksa dengan teknik PCR. Polimorfisme gen reseptor vitamin D Fok-1 diperiksa dengan teknil PCR-RFLP. Kadar 25(OH)D diperiksa menggunakan teknik ELISA. Hubungan antar variabel diuji dengan Fisher exact (p<0,05). Hasil: frekuensi genotipe dan alel RVD Fok-1 adalah CC (42%), CT (42%), TT (16%). Jumlah alel C (63%) dan alel T (37%). Rerata kadar vitamin D pada subjek penelitian adalah sebesar 28,16 (27,93(±8,69)) ng/ml. Frekuensi subjek penelitian berdasarkan kategori defisiensi (14%), insufisiensi (38%) dan sufisiensi (48%). Rerata indeks proliferasi sel (Ki-67) sebesar 21,7(±14,48)%, dengan frekuensi masing-masing kelompok grade +/-(18%); Grade 1+ (50%); grade 2+(30%), grade 3+ (2%). Tidak terdapat hubungan yang signifikan antara ketiga variabel : (1) Polimorfisme Fok-1 dengan kadar 25(OH)D (p=0,139); (2) Kadar 25(OH)D dengan indeks proliferasi imunohistokimia Ki-67 (p=0,082); (3) Polimorfisme Fok-1 dengan indeks proliferasi imunohistokimia Ki-67 ( p=0,285) Kesimpulan: tidak terdapat hubungan yang signifikan antara polimorfisme gen reseptor vitamin D Fok-1 (rs2228570) dan kadar vitamin D plasma terhadap proliferasi sel (Ki-67) pada kanker payudara

Introduction: Breast cancer is one of the serious health problems in women. In its activity vitamin D receptor along with its vitamin D ligand plays a role in breast cancer. Fok-1 is one of the vitamin D receptor polymorphisms in start codon area in exon 2, the conversion of bases (C> T) to produce a protein product of different lengths. Changes in vitamin D receptors may cause cellular changes by vitamin D that may affect the progression of tumor cells measured by cell prolifereation (Ki-67) in breast cancer Objective: to determine the association of vitamin D receptor gene polymorphism Fok-1 (rs2228570) and plasma vitamin D levels to proliferation ) of breast cancer cell (Ki-67) Methods: blood samples taken from 50 new cases of breast cancer patients and have not had chemotherapy since October 2017 to February 2018 at RSUP H. Adam Malik Medan. DNA isolation and gene amplification were examined by PCR technique. The polymorphism of the vitamin D receptor gene Fok-1 was examined by PCR-RFLP technique. Levels of 25(OH)D were examined using ELISA techniques. Relationships between variables were tested with Fisher exact (p <0.05). Results: genotypic frequency and RVD Fok-1 alleles were CC (42%), CT (42%), TT (16%). Number of C allele (63%) and T allele (37%). The mean vitamin D level in the study was 28.16 (27.93 (± 8.69)) ng/ml. Frequency of study subjects by category of deficiency (14%), insufficiency (38%) and sufisiensi (48%). The mean value of cell proliferation (Ki-67) was 21,7 (± 14,48)%, with frequency of each group: Grade +/- (18%); Grade 1+ (50%); grade 2+ (30%), grade 3+ (2%). There was no significant relationship between the three variables: (1) Fok-1 polymorphism with levels of 25(OH)D (p=0.139); (2) 25(OH)D levels with immunohistochemical expression of Ki-67 (p=0.082); (3) Fok-1 polymorphism with cell proliferation (Ki-67) (p 0.285) Conclusion: there is no significant association of vitamin D receptor gene polymorphism Fok-1 (rs2228570) and plasma vitamin D levels to proliferation ) of breast cancer cell (Ki-67)