Pharmacogenetics of advanced lung cancer: Predictive value of functional genetic polymorphism AGXT Pro11Leu in clinical outcome?
Maria Joana Catarata,
Margarida Lourenço,
Maria Fátima Martins,
João Frade,
Alice Pêgo,
Carlos Robalo Cordeiro,
Rui Medeiros,
Ricardo Ribeiro
Affiliations
Maria Joana Catarata
i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; Tumour & Microenvironment Interactions Group, INEB, Biomedical Engineering Institute, University of Porto, Portugal; Department of Pulmonology, University Hospital of Coimbra, Portugal; Faculty of Medicine, University of Porto, Portugal; Molecular Oncology and Viral Pathology Group - Research Centre, Portuguese Institute of Oncology, Porto, Portugal; Corresponding author at: i3S, Instituto de Investigação e Inovação em Saúde, Tumour & Microenvironment Interactions Group R. Alfredo Allen, 4200-135 Porto, Portugal.
Margarida Lourenço
Department of Clinical Pathology, University Hospital of Coimbra, Portugal
Maria Fátima Martins
Department of Clinical Pathology, University Hospital of Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Portugal
João Frade
Department of Clinical Pathology, University Hospital of Coimbra, Portugal
Alice Pêgo
Department of Pulmonology, University Hospital of Coimbra, Portugal
Carlos Robalo Cordeiro
Department of Pulmonology, University Hospital of Coimbra, Portugal; Faculty of Medicine, University of Coimbra, Portugal
Rui Medeiros
Faculty of Medicine, University of Porto, Portugal; Molecular Oncology and Viral Pathology Group - Research Centre, Portuguese Institute of Oncology, Porto, Portugal
Ricardo Ribeiro
i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; Tumour & Microenvironment Interactions Group, INEB, Biomedical Engineering Institute, University of Porto, Portugal; Department of Clinical Pathology, University Hospital of Coimbra, Portugal; Laboratory of Genetics, Faculty of Medicine, University of Lisbon, Portugal
Introduction: AGXT gene codes for the enzyme alanine glyoxylate aminotransferase, which is involved in hepatic peroxisomal metabolism of platinum-based chemotherapeutic agents. The association of genetic variant AGXT rs34116584 on the clinical outcome and response to chemotherapy of patients with non-small cell lung cancer (NSCLC) remains to be established. Our aim was to evaluate the association of functional AGXT gene polymorphism in NSCLC progression, considering as primary and secondary endpoint, progression free survival (PFS) and overall survival (OS), respectively. Methods: Genotyping of theAGXT rs34116584 genetic polymorphism was performed by mass spectrometry on 168 DNA samples from patients with NSCLC (stages IIIA-IVB). Univariate survival analysis included the study of Kaplan-Meier curves with the Log-Rank test, while Cox regression was used as a multivariate analysis. Results: Multivariate analysis showed shorter PFS for T carriers [HR = 2.0, 95% CI, 1.4−3.0, p < 0.0001] and shorter OS [HR = 1.8, 95% CI, 1.1−3.0, p = 0.017] globally, as well as in a subgroup of patients (n = 144) treated with first line platinum-based chemotherapy [HR = 2.0, 95% CI, 1.3–3.1, p = 0.001] and [HR = 1.8, 95% CI, 1.1–3.1, p = 0.026], respectively. Conclusion: This polymorphism seems to have an impact on NSCLC progression, opening new perspectives for its inclusion as a pharmacogenetic predictor of response to platinum-based chemotherapy.
