MDR1 C3435T POLİMORFİZMİ: KOLOREKTAL KANSER RİSKİ İLE İLİŞKİSİ ÜZERİNE BİR ÖN ÇALIŞMA

Abstract

Amaç: Bir veya çoklu genetik mekanizmaların kombinasyonuyla oluşan heterojen bir hastalık olan kolorektal kanser (KRK) dünyada en sık görülen üçüncü kanserdir. P-glikoproteini (P-gp) kodlayan çoklu ilaç direnci geni-1 (Multiple drug resistance-1 (MDR1)) ilaçların biyoyararlanımı ve hücre toksisitesinde rol oynar. Bu çalışmada, Türk popülasyonunda MDR1 geni C3435T polimorfizmi ve KRK riski arasındaki olası ilişkiyi araştırmayı amaçladık. Gereç ve Yöntemler: Çalışmamıza KRK hastası (26 erkek, 17 kadın) 43 kişi ve 48 sağlıklı kontrol (34 erkek, 14 kadın) dahil edilmiştir. MDR1 C3435T genotipleri Restriksiyon Fragman Uzunluk Polimorfizmi RFUP) yöntemiyle belirlenmiştir. Bulgular: MDR1 C3435T genotiplerinin dağılımı açısından çalışma grupları arasında istatistiksel anlamlılık elde edilmiştir. KRK hasta grubunda MDR1 C3435T CC, TT ve CT genotiplerinin sıklığı sırasıyla %16,3, %32,6 ve %51,2 olarak bulunmuştur. Homozigot TT genotipi frekansı KRK hastalarında %32,6 bulunurken kontrollerde %14,6 (p=0,04; OR=2,82, 95% CI: 1,01-7,87) olarak tespit edilmiştir. Hastalar ve sağlıklı kontroller karşılaştırıldığında MDR1 C3435T polimorfizmi TT genotipi taşıyıcıları KRK gelişimi için 2,8 kat (p<0,05) artmış risk altında bulunmuştur. Sonuç: Sonuçlarımız MDR1 C3435T polimorfizminin Türk popülasyonunda KRK gelişimi için genetik risk faktörlerinden biri olabileceğini göstermektedir.

Keywords

• MDR1
• C3435T
• polimorfizm
• kolorektal kanser
• Türk popülasyonu

MDR1 C3435T POLYMORPHISM: A PRELIMINARY STUDY ON ITS RELATIONSHIP WITH THE RISK OF COLORECTAL CANCER

Abstract

Objective: Colorectal carcinoma (CRC) is the third most frequent cancer in the world and a heterogenious disease which aroze from one or a combination of different genetic mechanisms. The multiple drug resistance-1 (MDR1) gene which encodes P-glycoprotein (P-gp) plays a part in the bioavailability of drugs and cell toxicity. In the current study, we aimed to investigate the possible relation between the MDR1 gene C3435T polymorphism and CRC risk in the Turkish population. Material and Methods: Forty three patients (26 men, 17 women) with CRC and 48 healthy controls (34 men, 14 women) were included in the study. The MDR1 C3435T genotypes were determined by the Restriction Fragment Length Polymorphism (RFLP) method. Results: Statistical significance was obtained in terms of genotype distributions of MDR1 C3435T genotypes between study groups. The frequencies of MDR1 C3435T CC, TT and CT genotypes in the CRC patient group were found as 16.3%, 32.6% and 51.2%, respectively. The frequency of the homozygous TT genotype was found as 32.6% in CRC patients while it was identified as 14.6% in controls (p=0.04; OR=2.82, 95% CI: 1.01-7.87). When the patients were compared with the healthy population, TT genotype carriers of MDR1 C3435T polymorphism were found at 2.8-fold (p<0.05 ) increased risk for the development of CRC. Conclusion: Our results show that the MDR1 C3435T polymorphism might be one of the genetic risk factors for CRC development in the Turkish population.

Keywords

• MDR1
• C3435T
• polymorphism
• colorectal cancer
• Turkish population

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