Meta-analysis of genome-wide association studies for cancer therapy-related cardiovascular dysfunction and functional mapping highlight an intergenic region close to TP63
Year: 2024
Type: review
Study design: Observational Study
Abstract: Cancer therapy-related cardiac dysfunction (CTRCD), which commonly includes left ventricular dysfunction and heart failure, is the main adverse effect of anticancer therapy. In recent years several candidate genes studies and genome-wide association studies have identified common genetic variants associated with CTRCD, but evidence remains limited and few genetic variants are robust. A genome-wide meta-analysis of CTRCD was performed with 852 oncology patients receiving cancer therapy. DNA samples were genotyped and imputed to perform a GWAS meta-analysis for case–control (N = 852 (380 cases and 472 controls) and extreme phenotypes (N = 618 (78 cases and 472 controls) looking for genetic variants that predispose to CTRCD. The results were validated in a replicate cohort of 1,191 oncology patients (245 cases and 946 controls). Functional mapping of the replicated loci was then performed. The meta-analysis showed 9 and 17 loci suggestively associated ( P -value < 1 × 10 –5 ) with CTRCD in case–control and extreme phenotypes analyses, respectively. The 3q28 locus (rs rs7652759, P = 5.64 × 10 –6 ) in the case–control analysis was the strongest signal, with up to 64 SNPs above the suggestive significance threshold. The rs7652759, an intergenic variant between TPRG1 and TP63 genes, was the only variant validated in the replication cohort (P-value = 0.01). Functional mapping of this significant locus revealed up to 5 new genes potentially involved in the CTRCD. We identified the intergenic region near TP63 as a novel CTRCD susceptibility locus. In the future, the genotyping of these markers could be considered in new CTRCD risk scores to improve preventive strategies in cardio-oncology.
Source: Scientific Reports
Authors: L. Martínez-Campelo, A. Blanco-Verea, T. López-Fernández, A. Martínez-Monzonís, A. Buño, P. Mazón, P. Zamora, N. Norton, J. S. Reddy, A. Velasco-Ruiz, A. González-Neira, C. Vulsteke, T. Alonso-Gordoa, R. Cruz, S. Diz-de Almeida, A. Carracedo, JR. González-Juanatey, J. López-Sendón, M. Brion, The CardioTox registry investigators, José López Sendón, Antonio Buño Soto, Miguel Canales Albendea, Enrique Espinosa, Jaime Feliu Batlle, Teresa López-Fernández, Esteban López de Sá, Mar Moreno Yangüela, Elena Ramírez, Olaia Rodríguez Fraga, Investigators, Ainara Albaladejo, Guiomar Mediavilla, Carlos Álvarez-Ortega, Mar Moreno Yangüela, Silvia Valbuena, Regina Dalmau, Almudena Castro, Esteban López de Sá, Juan Caro Codón, Pilar Zamora Auñon, Jaime Feliu Batlle, Enrique Espinosa, Beatriz Castelo, Andrés Redondo, Álvaro Pinto, Miguel Canales Albendea, Pilar Gómez Prieto, Patricia Chanca, Paloma Oliver, Olaia Rodríguez Fraga, Isabel Rodríguez, Lara Miralles, Belén Belinchón, Aurea Manso, Rosa Moreiras, Gema Casado, Alicia Herrero, José González-Costello, Sonia Pernas Simón, José Ramón González-Juanatey, Pilar Mazón Ramos, Amparo Martínez Monzonis, Rafael López López, Patricia Palacios Ozores, Milagros Pedreira Pérez, Belén Álvarez Álvarez, Begoña Campos Balea, Carlos González-Juanatey, Ana Testa Fernández, Silvia Varela Ferreiro, José María Serrano Antolín, Juan Antonio Guerra Martínez, Luis Javier Morales García, Carlos Gutiérrez Landaluce, Elena Moreno Merino, Nieves Estival Ortega, Joaquín Alonso, Francisco Fernández Avilés, Ana González-Mansilla, Pilar García Alfonso, Rosalía Cadenas Chamorro, María Merino Salvador, Ignacio Plaza, Vicente Bertomeu, Juan Quiles
Institutions: Instituto de Investigación Sanitaria de Santiago, Hospital Universitario La Paz, Mayo Clinic in Florida, Mayo Clinic Comprehensive Cancer Center (Florida), Spanish National Cancer Research Centre, University of Antwerp, Hospital Universitario Ramón y Cajal, Universidade de Santiago de Compostela, Centro de Investigación Biomédica en Red, Fundación Pública Galega de Medicina Xenómica, Hospital La Paz Institute for Health Research, Institut d'Investigació Biomédica de Bellvitge, Hospital Universitario Lucus Augusti, Hospital Universitario de Fuenlabrada, Hospital General Universitario Gregorio Marañón, Hospital Universitario Infanta Sofía
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,590
Awards: G1201465284, Toxicidad cardiovascular por fármacos antitumorales. Valoración del riesgo y diagnostico precoz, G2014575872, Predicción de riesgo de cardiotoxicidad en la unidades de cardio-oncología. Valor de la genética y diferentes biomarcadores. El registro CARDIOTOX., Papel de los genes mitocondriales en el desarrollo de cardiotoxicidad: identificación de biomarcadores predictivos, Evaluación genética de la cardiotoxicidad inducida por quimioterapia: Estudio de asociación de genoma completo y secuenciación de exoma de individuos con fenotipo más severo, Individualized medicine to predict and prevent chemotherapy-related heart failure
OpenAlex ID: W4401424462