Investigation of the GSTP1 C341T polymorphism in patients with Cirrhosis and hepatocellular Carcinoma

• Grant number: 12/11847-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): September 01, 2012
• Effective date (End): August 31, 2013
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Eny Maria Goloni Bertollo
• Grantee: Pamela Risardi Francelin
• Host Institution: Faculdade de Medicina de São José do Rio Preto (FAMERP). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São José do Rio Preto , SP, Brazil

Abstract

Hepatocellular carcinoma (HCC) is the most frequent primary tumor of the liver. The main risk factors include chronic viral infection by HBV and HCV, cirrhosis, alcoholic liver disease / non-alcoholic, and hereditary genetic disorders such as Wilson disease and hemochromatosis. Such diseases are related to molecular events that induce hepatocellular carcinogenesis since they can interfere with DNA synthesis. Polymorphisms in xenobiotic-metabolizing genes, such as family members' glutathione S-transferases (GSTs) may lead to increased activation of carcinogens or decreased ability to inactivate them may increase the risk for cancer. This study aims to analyze the C341T polymorphism of the GSTP1 gene in patients with cirrhosis and hepatocellular carcinoma and in individuals with no history of cancer (control group), to identify biomarkers of susceptibility to this cancer. In this proposal, we will evaluate 150 patients with a pathologic diagnosis of cirrhosis or hepatocellular carcinoma and blood samples from 500 healthy controls. Some variables also will be analyzed: age, hepatitis B virus, hepatitis C, elitism, cirrhosis, diabetes mellitus, BMI (body mass ondex), and level of alpha-fetoprotein. polymorphisms genotyping will be performed by PCR-RFLP technique. The molecular findings and information about risk factors will be evaluated statistically. The results may help to clarify the role of genetic differences in susceptibility to the effects of carcinogens and identify biomarkers of susceptibility.(AU)