Development of a rapid and inexpensive genetic test for the detection of variants in the dihydropyrimidine dehydrogenase (DPYD) gene

• Grant number: 21/10524-3
• Support Opportunities: Scholarships abroad - Research
• Start date: November 16, 2021
• End date: January 15, 2022
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Eder de Carvalho Pincinato
• Grantee: Eder de Carvalho Pincinato
• Host Investigator: Luis Andrés López Fernández
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Spain

Abstract

Fluoropyrimidines are chemotherapic drugs indicated for the treatment of colorectal, breast, or stomach cancer. It is a widely used drug, however, more than 30% of treated patients develop adverse events such as diarrhea, neutropenia, and hand-foot syndrome. The DPYD gene codes for the enzyme dihydropyrimidine dehydrogenase (DPD), which is responsible for catalyzing the reaction of transformation of pyrimidines into dihydropyridines, thus, a deficiency of this enzyme is associated with more serious and frequent adverse events. Previous analyzes of the DPYD gene are beneficial to patients, as they help to reduce serious adverse events and deaths, without increasing costs, as they prevent toxicities and avoid the costs of hospitalizations, additional tests, and new treatments. Therefore, this study aims to develop an alternative method for genotyping the main variants of the DPYD gene that allows the rapid, sensitive and cost-effective detection of patients at risk of developing toxicity before starting treatment and that can be adapted to other genetic alterations. (AU)