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Post-GWAS study for the 2q22 risk region for renal cancer

Grant number: 22/12980-9
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): May 01, 2023
Effective date (End): April 30, 2025
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Leandro Machado Colli
Grantee:Aline Gomes de Souza
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:20/10960-5 - Renal cancer genetic susceptibility, AP.JP

Abstract

Renal cancer is the seventh most common type of cancer and shows a growing increase in the number of new cases, especially in Brazil. GWAS (Genome-Wide Association Study) studies have been applied to identify single nucleotide polymorphisms (SNPs) in chromosomal regions at risk for the development of this disease. From such studies, 13 different risk regions have been identified for renal cancer, but in only three the molecular mechanism of risk is understood. Understanding these mechanisms may reveal new oncogenic pathways and different treatment approaches for this neoplasm. Thus, to accelerate these studies, our group used five other functional screening techniques (MPRA, ChiP-seq, ATAC-seq, Capture-HiC, and eQTL) to identify SNPs and candidate genes. In this study, we aimed to identify the biological mechanism that drives the risk of developing RCC in the 2q22 region (odds ratio = 1.3; p-value = 1.80 × 108). In this way, we will seek to identify the functional SNP(s) in the 2q22 region from the data already generated by our group, as well as functional assays of luciferase, EMSA, and ChIP-seq. We will also evaluate the impact of genes associated with these SNPs on renal oncogenesis using cell culture and animal models. Thus, we hope to understand the molecular and oncological mechanisms linked to this 2q22 region that may contribute to a better understanding of kidney cancer, which may impact the treatment and prognosis of patients with this disease.

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