The role of polymorphisms in VEGF and VEGFR2 genes, related to angiogenesis, in clinical features, and prognosis of Diffuse Large B Cell Lymphoma patients

• Grant number: 15/15756-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): November 01, 2015
• Effective date (End): October 31, 2016
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Carmen Silvia Passos Lima
• Grantee: Angelo Borsarelli Carvalho de Brito
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Angiogenesis (AG) is the process of vessels formation. AG is important in the development of hematologic malignancies, including diffuse large B-cell lymphoma (DLBCL). Two key proteins are involved in AG: the "vascular endothelial growth factor" (VEGF) and the "vascular endothelial growth factor receptor 2" (VEGFR2). Such proteins are translated by VEGF and VEGFR2 genes, which are polymorphic in humans. The aim of this study is to assess the roles of the polymorphisms -2578C / A (rs699947), -2489C / T (rs1005230), -1154G / A (rs1570360), -634G / C (rs2010963), -460 C / T ( rs833061) and + 936C / T (rs3025039) of the VEGF gene and -271G / A (rs7667298), -604T / C (rs2071559), +1192 G / A (rs2305948), and + 1719A / T (rs1870377) in the gene VEGFR2 in clinical, biological characteristics of the tumor and the prognosis of DLBCL patients. It will be evaluated 150 consecutive patients with DLBCL treated at the Hematology and Hemotherapy Center of the University of Campinas (Unicamp) and the AC Camargo Cancer Center. Clinical data and the tumor will be obtained from the biorepository of Cancer Genetics Laboratory of UNICAMP. The genotypes of such polymorphisms will be identified by real-time polymerase chain reaction using the TaqMan system. Statistical significance of differences between groups of patients stratified by clinical and biological characteristics of the tumor and genotypes will be assessed through tests or Fisher exact probability of Chi-square and multiple logistic regression. The impact of age, gender, ethnicity, bone marrow involvement by tumor, tumor Ki-67 proliferation index, tumor stage, International Prognostic Index (IPI), the pattern of response to therapy and genetic polymorphisms in free survival disease progression (PFS), and overall survival (OS) of patients will be assessed by Kaplan-Meier and univariate and multivariate Cox analysis. The analysis will be performed with SPSS 15.0 (SPSS Inc., IL, USA). We hope, at the end of the study, to contribute to the understanding of the role of inherited ability to form vessels in tumor pathophysiology. We also hope to characterize groups of patients with different prognoses, which may merit different therapeutic in the modern concept of personalized oncology.(AU)