PPAR-alpha L162V polymorphism in human hepatocellular carcinoma

Amaç: Hepatosellüler kanserlerin gelişiminde PPARα ’nın rolüne işaret eden birçok kanıt mevcuttur. PPARα geninin L162V polimorfizmi bu transkripsiyon faktörünün transaktivasyonunu arttırır. Bu çalışmanın amacı hepatit virüsü enfeksiyonu zemininde gelişmiş hepatosellüler kanser hastalarında PPAR· L162V polimorfizminin sıklığının ve bu mutasyonun klinik seyir ile ilişkisinin araştırmasıdır. Yöntem: Ankara Üniversitesi Gastroenteroloji Kliniğinde Ocak 2002 – Temmuz 2003 tarihleri arasında tanı almış ve 90 hepatosellüler kanserlerin hastası ve 80 sağlıklı kontrol (normal beden kitle indeksi, kan biyokimyası olan ve viral serolojisi negatif olan) çalışmaya alındı. PPAR· L162V polimorfizmi PZR-RFLP yöntemi ile tespit edildi. Bulgular: Hastaların etyolojileri, 56 HBV, 12 HBV+HDV, 22 HCV olarak tespit edildi. 87 hasta(%97) sirotikti ve 60 hastanı n (%67.5) tümörü ileri evredeydi. 83 hastada (%92-50 HBV, 12 HBV+HDV, 21 HCV) PPAR· geninin polimorfik bölgesini PZR ile amplifiye edilebildi. Bu hastaların 6’sında (%7,2- tamamı HBV) L162V polimorfizmi tespit edilirken, kontrol hastaları nın 2’sinde (%2,5-p=0,162) bu polimorfizm tespit edildi. Bu trendin HBV+HDV olan hastalar ile kontroller karşılaştırıldı- ğında daha belirgin olduğu (6/62, %9.2 – 2/80 %2.5, p=0.071). L162V polimorfizmi olan hastalardan 5 ‘inde ileri evre hastalık mevcuttur. Sonuç: PPAR· geninin L162V polimorfizmi HBV ile ilişkili hepatosellüler kanserde görülürken HCV zemininde gelişenlerde görülmemektedir. Bu bulgular farklı iki etyoloji zemininde gelişen hepatosellüler kanserlerin karsinogenetik mekanizmaları n farklı olabileceğini düşündürmektedir. L162V polimorfizmi olan hastalardaki Hepatosellüler kanserin ileri evrede olması bu polimorfizmin hastalığın progresyonunu etkilediğ ini düşündürmektedir.

Anahtar Kelime: Hepatit B, kronik Peroksizom prolifetör-aktive reseptörler Polimeraz zincir reaksiyonu Polimorfizm, kesim parçacığı uzunluk Karsinom, hepatosellüler Olgu-kontrol çalışmaları Karaciğer neoplazmları Hepatit C, kronik Polimorfizm, genetik

Konular: Cerrahi

Hepatosellüler kanserde PPARα L162V polimorfizmi

Öz:

Background/aims: Several lines of evidence suggest that peroxisome proliferator-activated receptor alpha may be involved in hepatocarcinogenesis. L162V polymorphism of the peroxisome proliferator-activated receptor alpha gene enhances the transactivation activity of this transcription factor. The aim of this study was to determine the frequency and clinical correlates of peroxisome proliferator-activated receptor alpha L162V polymorphism in hepatitis virus-induced hepatocellular carcinoma. Methods: 90 hepatocellular carcinoma patients diagnosed at Ankara University Gastroenterology Clinic between January 2002 and July 2003 and 80 healthy controls with normal body mass index, blood chemistry and with negative viral serology were included. peroxisome proliferator-activated receptor alpha L162V polymorphism was determined by PCR-RFLP. Results: hepatocellular carcinoma etiologies were as follows: 56 HBV, 12 HBV+HDV, 22 HCV. Eighty-seven patients (97%) were cirrhotic, and 60 patients (67.5%) had advanced tumors. In 83 (92%) of 90 hepatocellular carcinoma patients, gene segment including polymorphic region could be amplified by PCR (50 HBV, 12 HBV+HDV, 21 HCV) and 6 of them (7.2%, all infected with HBV) had L162V polymorphism, while 2 (2.5%) of 80 controls had this polymorphism (p=0.162). This trend became more remarkable when only HBV (HBV+HDV)-infected patients were compared with controls (6/62, 9.7% vs. 2/80, 2.5%, respectively, p=0.071). Five of 6 patients with L162V had advanced disease. Conclusions: Peroxisome proliferator-activated receptor alpha L162V polymorphism tends to occur in HBV-induced epatocellular carcinoma and is absent in HCV-related epatocellular carcinoma. These findings may show clues for the existence of different carcinogenesis mechanisms in these two common etiologies. Frequent occurrence of advanced disease in patients with L162V polymorphism suggests a role for this polymorphism in tumor progression.

Anahtar Kelime: Case-Control Studies Liver Neoplasms Hepatitis C, Chronic Polymorphism, Genetic Hepatitis B, Chronic Peroxisome Proliferator-Activated Receptors Polymerase Chain Reaction Polymorphism, Restriction Fragment Length Carcinoma, Hepatocellular

Konular: Cerrahi

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

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APA	KOYTAK E, MIZRAK D, BEKTAŞ M, VERDI H, ARSLAN ERGÜL A, İDİLMAN R, Çınar K, YURDAYDIN C, Ersöz S, KARAYALÇIN K, UZUNALİMOĞLU Ö, BOZKAYA H (2008). PPAR-alpha L162V polymorphism in human hepatocellular carcinoma. , 245 - 249.
Chicago	KOYTAK Elif Sare,MIZRAK Dilşa,BEKTAŞ Mehmet,VERDI HASIBE,ARSLAN ERGÜL AYÇA,İDİLMAN Ramazan,Çınar Kubilay,YURDAYDIN Cihan,Ersöz Sadık,KARAYALÇIN Kaan,UZUNALİMOĞLU Özden,BOZKAYA Hakan PPAR-alpha L162V polymorphism in human hepatocellular carcinoma. (2008): 245 - 249.
MLA	KOYTAK Elif Sare,MIZRAK Dilşa,BEKTAŞ Mehmet,VERDI HASIBE,ARSLAN ERGÜL AYÇA,İDİLMAN Ramazan,Çınar Kubilay,YURDAYDIN Cihan,Ersöz Sadık,KARAYALÇIN Kaan,UZUNALİMOĞLU Özden,BOZKAYA Hakan PPAR-alpha L162V polymorphism in human hepatocellular carcinoma. , 2008, ss.245 - 249.
AMA	KOYTAK E,MIZRAK D,BEKTAŞ M,VERDI H,ARSLAN ERGÜL A,İDİLMAN R,Çınar K,YURDAYDIN C,Ersöz S,KARAYALÇIN K,UZUNALİMOĞLU Ö,BOZKAYA H PPAR-alpha L162V polymorphism in human hepatocellular carcinoma. . 2008; 245 - 249.
Vancouver	KOYTAK E,MIZRAK D,BEKTAŞ M,VERDI H,ARSLAN ERGÜL A,İDİLMAN R,Çınar K,YURDAYDIN C,Ersöz S,KARAYALÇIN K,UZUNALİMOĞLU Ö,BOZKAYA H PPAR-alpha L162V polymorphism in human hepatocellular carcinoma. . 2008; 245 - 249.
IEEE	KOYTAK E,MIZRAK D,BEKTAŞ M,VERDI H,ARSLAN ERGÜL A,İDİLMAN R,Çınar K,YURDAYDIN C,Ersöz S,KARAYALÇIN K,UZUNALİMOĞLU Ö,BOZKAYA H "PPAR-alpha L162V polymorphism in human hepatocellular carcinoma." , ss.245 - 249, 2008.
ISNAD	KOYTAK, Elif Sare vd. "PPAR-alpha L162V polymorphism in human hepatocellular carcinoma". (2008), 245-249.

APA	KOYTAK E, MIZRAK D, BEKTAŞ M, VERDI H, ARSLAN ERGÜL A, İDİLMAN R, Çınar K, YURDAYDIN C, Ersöz S, KARAYALÇIN K, UZUNALİMOĞLU Ö, BOZKAYA H (2008). PPAR-alpha L162V polymorphism in human hepatocellular carcinoma. Turkish Journal of Gastroenterology, 19(4), 245 - 249.
Chicago	KOYTAK Elif Sare,MIZRAK Dilşa,BEKTAŞ Mehmet,VERDI HASIBE,ARSLAN ERGÜL AYÇA,İDİLMAN Ramazan,Çınar Kubilay,YURDAYDIN Cihan,Ersöz Sadık,KARAYALÇIN Kaan,UZUNALİMOĞLU Özden,BOZKAYA Hakan PPAR-alpha L162V polymorphism in human hepatocellular carcinoma. Turkish Journal of Gastroenterology 19, no.4 (2008): 245 - 249.
MLA	KOYTAK Elif Sare,MIZRAK Dilşa,BEKTAŞ Mehmet,VERDI HASIBE,ARSLAN ERGÜL AYÇA,İDİLMAN Ramazan,Çınar Kubilay,YURDAYDIN Cihan,Ersöz Sadık,KARAYALÇIN Kaan,UZUNALİMOĞLU Özden,BOZKAYA Hakan PPAR-alpha L162V polymorphism in human hepatocellular carcinoma. Turkish Journal of Gastroenterology, vol.19, no.4, 2008, ss.245 - 249.
AMA	KOYTAK E,MIZRAK D,BEKTAŞ M,VERDI H,ARSLAN ERGÜL A,İDİLMAN R,Çınar K,YURDAYDIN C,Ersöz S,KARAYALÇIN K,UZUNALİMOĞLU Ö,BOZKAYA H PPAR-alpha L162V polymorphism in human hepatocellular carcinoma. Turkish Journal of Gastroenterology. 2008; 19(4): 245 - 249.
Vancouver	KOYTAK E,MIZRAK D,BEKTAŞ M,VERDI H,ARSLAN ERGÜL A,İDİLMAN R,Çınar K,YURDAYDIN C,Ersöz S,KARAYALÇIN K,UZUNALİMOĞLU Ö,BOZKAYA H PPAR-alpha L162V polymorphism in human hepatocellular carcinoma. Turkish Journal of Gastroenterology. 2008; 19(4): 245 - 249.
IEEE	KOYTAK E,MIZRAK D,BEKTAŞ M,VERDI H,ARSLAN ERGÜL A,İDİLMAN R,Çınar K,YURDAYDIN C,Ersöz S,KARAYALÇIN K,UZUNALİMOĞLU Ö,BOZKAYA H "PPAR-alpha L162V polymorphism in human hepatocellular carcinoma." Turkish Journal of Gastroenterology, 19, ss.245 - 249, 2008.
ISNAD	KOYTAK, Elif Sare vd. "PPAR-alpha L162V polymorphism in human hepatocellular carcinoma". Turkish Journal of Gastroenterology 19/4 (2008), 245-249.