CYP2C9 VE VKORC1 GENLERİNİN PROSTAT KANSERİ ETYOLOJİSİNDEKİ ROLLERİNİN ARAŞTIRILMASI

1. Amaç: Çalışmamızda, Sitokrom p450 enzimlerini kodlayan CYP ve vitamin K epoksit redüktaz kompleks subünit1 enzimini kodlayan VKORC1 genlerinin alt gruplarındaki tek nükleotit polimorfizmlerinin muhtemel bireysel ve ortak etkilerini prostat kanseri hastalarında araştırmayı amaçladık. Çalışma sonuçları aynı zamanda bu iki gen ile ilgili henüz ortaya konmamış olan bizim populasyonumuza özgü genotip dağılımını da kısmen ortaya koyacaktır. 2. Gereç ve Yöntem: Çalışmamıza 48 prostat kanseri tanılı erkek hasta ve 48 sağlıklı erkek birey dâhil edildi. Hasta grubu prostat tanısı almış yaş aralığı 49-86 olan gönüllü bireylerden seçildi. Kontrol grubu prostat kanseri olmadığı belirlenmiş, 51-86 yaş grubundaki gönüllü bireylerden seçildi. Hasta ve kontrol grubu bireylerinin venöz kanları alınarak genomik DNA izolasyonları yapıldı. İzole edilen DNA’ların ilgili gen bölgeleri polimeraz zincir reaksiyonu (PCR) ile çoğaltıldı. Sonrasında PCR ürünleri mikroarray cihazında özel problar yardımıyla çalışıldı. CYP2C9 ve VKORC1 gen bölgelerine ait alt grupların polimorfizmleri tanımlandı ve EpiInfo 3.5.1 istatistik programı ile anlamlılıkları hesaplandı. 3. Bulgular: Sonuçlarımızda CYP2C9 ve VKORC1 enzimlerini kodlayan genlerin alt gruplarının polimorfizmleri karşılaştırıldığında hasta ve kontrol grubu arasında yüzde olarak önemli farklar görüldü. Örneğin VKORC1 6853 G>C polimorfizmi için kontrol grubunda CC alleli %25 iken hasta grubunda %34,5 olarak tespit edildi. CYP2C9 *3 A>C değişimi için kontrol grubunda CC alleli %79,16 iken hasta grubunda %87,5 olarak tespit edildi. 4. Sonuç: Çalışmamızda sayı ve yüzde olarak hasta ve kontrol grubunda önemli farklar görüldü. CYP2C9 ve VKORC1 geninin alt gruplarının analizleri sonucunda istatistiksel anlamlılık tespit edilmedi. Bunun sebebinin örnek sayısı azlığı ile alakalı olduğu düşünüldü ve ileri çalışmaların konuyu aydınlatacağı düşünüldü.

Anahtar Kelimeler:

VKORC1, CYP2C9, Sitokrom p450, Prostat, kanser

The Role of Genes CYP2C9 and VKORC1 in the Ethiology of Prostate Cancer

1. Objective: In our study, we aimed to investigate possible individual and common effects of single nucleotide polymorphisms of the gene encoding the enzyme cytochrome p450 (CYP) and the gene encoding the enzyme vitamine K epoxide reductase complex subunit 1 (VKORC1) and their subgroups in patients with prostate cancer. The results of the study also will partially reveal the distribution of genotypes specific to our population, which have not yet been addressed in relation to these two genes.2. Methods: 48 prostate cancer diagnosed patients and 48 healty male individuals were included in our study. The patient group was selected from volunteers with a prostate-diagnosed age range of 49-86. The control group was selected among without prostate cancer and aged 51-86 years individual. Venous blood was taken from all individuals. Targeted regions were amplified by polymerase chain reaction (PCR) from isolated DNAs. PCR products were genotyped using microarray with appropriate DNA probes. Polymorphisms in the subgroups of the CYP2C9 and VKORC1 gene regions were identified. The results were calculated using the EpiInfo 3.5.1 statistical program.3. Result: The percentages between patient and control groups showed significant differences when the subgroup polymorphisms of genes encoding CYP2C9 and VKORC1 enzymes were compared. For example, the CC allele of VKORC1 6853 G> C polymorphism found to be %25 in the control and %34.5 in the patient group. The CC allele of CYP2C9 * 3 A> C change found %79.16 in the control and %87.5 in the patient group. 4. Conclusion: Significant differences were seen in number and percentage of patients and control groups in our study. As a result of analysis of the subgroups of CYP2C9 gene and of the VKORC1 gene, statistical significance was not observed. But the percentage results show important differences, though we expect statistical significiance when the numbers of individual is increased

Keywords:

VKORC1, CYP2C9, Cytochrome p450, Prostate,

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