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Gene expression and haplotypes of genes involved in cell signaling and the risk for hepatocellular carcinoma

Grant number: 13/21622-0
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): July 01, 2014
Effective date (End): March 31, 2015
Field of knowledge:Health Sciences - Medicine
Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Dorotéia Rossi Silva Souza
Grantee:Graciele Domitila Tenani
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 aggressive form of liver cancer, accounting for 90% of cases of primary liver cancer. The risk factors for HCC include hepatitis C and B, alcoholic cirrhosis, prolonged exposure to aflatoxin, hereditary metabolic diseases besides genetics changes that can affect many cellular pathways acting in carcinogenic process. Objectives - Evaluate the gene expression of Phosphatidylinositol-4-5 bifosfato 3-kinase (Alpha catalytic subunit) (PIK3CA) and Phosphatase and angiotensin Homolog (PTEN) in liver tissue of patients with HCC and control individuals. Analyse the association between the expression of PTEN gene and single nucleotide polymorphisms (rs10490920, rs532678, rs701848) in HCC patients and control subjects, as well as analyze the reason of chance for HCC development by evaluating the haplotypes of PTEN gene. Methods - 340 individuals will be selected, regardless of sex, ethnicity and age, which will be divided into two groups for polymorphisms analysis: group 1- 170 individuals diagnosed with HCC and group 2- 170 control individuals, without clinical and biochemical signs of HCC. Among these individuals, we will selected 30 individuals from each group for the analysis of tissue gene expression of the PIK3CA and PTEN. The polymorphisms analysis will be performed by Polymerase Chain Reaction (PCR) followed by Restriction Fragment Length Polymorphism (RFLP) and gene expression by Real-Time PCR. Statistical analysis will use T test, Fisher's exact test or chi-square test and multivariate regression with significance level for p<0.05. The haplotypes will be rebuilt according to the genotyping of patients and controls with frequency >0.05. (AU)

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