Pharmacogenetics of advanced lung cancer: Predictive value of functional genetic polymorphism AGXT Pro11Leu in clinical outcome?

Autor: Maria Joana Catarata, Ricardo Ribeiro, Margarida Lourenço, Rui Medeiros, Maria de Fátima Martins, Alice Pêgo, João Gonçalo Frade, Carlos Robalo Cordeiro
Přispěvatelé: Instituto de Investigação e Inovação em Saúde
Rok vydání: 2020
Předmět:
Pulmonary and Respiratory Medicine
Oncology
Male
medicine.medical_specialty
Lung Neoplasms
Genotype
Single-nucleotide polymorphism
Antineoplastic Agents
Severity of Illness Index
Carboplatin
03 medical and health sciences
0302 clinical medicine
Non-small cell lung cancer
Polymorphism (computer science)
Predictive Value of Tests
Internal medicine
Carcinoma
Non-Small-Cell Lung
medicine
Humans
030212 general & internal medicine
Progression-free survival
Lung cancer
Survival analysis
Transaminases
Aged
Neoplasm Staging
Retrospective Studies
lcsh:RC705-779
Polymorphism
Genetic
business.industry
Proportional hazards model
lcsh:Diseases of the respiratory system
Middle Aged
medicine.disease
Prognosis
Progression-Free Survival
Single nucleotide polymorphism
030228 respiratory system
Pharmacogenetics
Disease Progression
Female
Gene polymorphism
Cisplatin
business
Cohort study
Zdroj: Pulmonology, Vol 27, Iss 2, Pp 116-123 (2021)
ISSN: 2531-0437
Popis: 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. MJ Catarata was supported by the Portuguese Pulmonology Society .
Databáze: OpenAIRE
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