Analysis of the influence of polymorphisms in the OPRM1 gene on the effectiveness and safety of opioids in patients with lung cancer.

• Grant number: 24/10377-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2024
• End date: September 30, 2025
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Patricia Moriel
• Grantee: José Augusto Sakae Defende
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Pain is one of the most frequently reported symptoms by lung cancer patients. Opioids are frequently used to manage oncological pain. However, there is considerable interindividual variability in the response to opioids, which can result in ineffectiveness or adverse drug reactions (ADRs). This variability can have various causes, including genetic variability in the OPRM1 gene, which encodes the therapeutic target of opioids. The aim of this study is to evaluate the association between variants in the OPRM1 gene and the effectiveness and safety of opioid treatment in lung cancer patients experiencing chronic pain. Patients will be recruited from the OncoPneumology Clinic, located at the Hospital de Clínicas of the University of Campinas, and will be divided into two groups: Group 1, patients prescribed acetaminophen + codeine (PACO); and Group 2, patients who initially received PACO but had their therapy switched to morphine due to lack of response or ADRs. Biodemographic data, treatment history, and ADR history will be collected. Effectiveness will be measured using the numeric visual scale (NVS) for pain, and safety will be assessed based on the development of ADRs. Patients will be followed prospectively for 3 months. For genotyping, genomic DNA will be extracted using the QIAamp® DNA Blood Maxi Kit (QIAGEN, GmbH, Germany). Whole genome genotyping will be performed by microarray using the iScan System (Illumina, San Diego, California, USA) with the Infinium Global Diversity Array with Enhancer PGx kit (Illumina, San Diego, California, USA). Group 1 will be compared with Group 2 regarding therapeutic response, frequency of ADRs, and frequency of genetic variants.