PPAR-alpha L162V polymorphism in human hepatocellular carcinoma.
OBJECTIVE
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 hepatocellular carcinoma and is absent in HCV-related hepatocellular 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.
Koytak
Elif Sare
ES
Departments of Gastroenterology and General Surgery, Ankara University, School of Medicine, Ankara.
Mizrak
Dilşa
D
Bektaş
Mehmet
M
Verdi
Hasibe
H
Arslan Ergül
Ayça
A
Idilman
Ramazan
R
Cinar
Kubilay
K
Yurdaydin
Cihan
C
Ersõz
Sadik
S
Karayalçin
Kaan
K
Uzunalimoğlu
Ozden
O
Bozkaya
Hakan
H
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology*; D016022:Case-Control Studies; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications*; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology*; D008297:Male; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
D047492:Peroxisome Proliferator-Activated Receptors