PPAR-alpha L162V polymorphism in human hepatocellular carcinoma

Date
2008
Advisor
Instructor
Source Title
Turkish Journal of Gastroenterology
Print ISSN
1300-4948
Electronic ISSN
Publisher
Turkish Society of Gastroenterology
Volume
19
Issue
4
Pages
245 - 249
Language
English
Type
Conference Paper
Journal Title
Journal ISSN
Volume Title
Abstract

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.

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Book Title
Keywords
Hepatitis B virus, Hepatitis C virus, Hepatocellular carcinoma, L162V, Polymorphism, PPARα, Cancer diagnosis, Cancer staging, DNA polymorphism, Hepatitis delta virus, Liver cell carcinoma, Liver cirrhosis, Major clinical study, Pathogenesis, Polymerase chain reaction, Restriction fragment length polymorphism, Liver neoplasms
Citation
Published Version (Please cite this version)