POLYGENIC RISK SCORES OF CISPLATIN-MEDIATED TOXICITY

• Grant number: 19/17040-1
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: November 01, 2019
• End date: October 31, 2020
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Patricia Moriel
• Grantee: Maria Aparecida Cursino
• Supervisor: Munir Hussein Pirmohamed
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: University of Liverpool, England
• Associated to the scholarship: 17/17245-7 - Polymorphism analysis of the CYP2E1, ABCB1, ABCC2, OCT2 and MATE1 genes involved in the major adverse effects of cisplatin treatment of the Head and Neck Cancer, BP.DR

Abstract

Cisplatin is a highly effective antineoplastic agent, widely used in the treatment of various malignant tumors, in adults and pediatrics. Despite being effective, toxicity can limits its use. Ototoxicity mediated by cisplatin is irreversible and, in children, it is very important because of the impact on their speech-language acquisition development, social-emotional development, and learning difficulties, while nephrotoxicity leads to important morbidity. Nephrotoxicity is reversible in some cases, and studies show that the prevalence of renal adverse effects in children, after cisplatin cancer treatment, ranged from 10% to 80%. While current clinical and biochemical biomarkers of kidney injury exist, none are standardized or validated to the severity of, recovery from or long-term prognosis of cisplatin-nephrotoxicity and novel biomarkers exist but they are still not clinically validated and integrated to pediatric routine. In this context, we aim to investigate whether there are genetic factors associated to nephrotoxicity in pediatric patients receiving cisplatin. Secondary objective is measuring potential new kidney function biomarkers and compare with currently used clinical biomarkers. The study population comprises approximately 400 children from the MAGIC study. Genome-wide association analysis and polygenic risk scores will be used to identify genetic variants associated to cisplatin-induced nephrotoxicity in pediatric patients treated with cisplatin.