Pharmacogenetics of advanced lung cancer: Predictive value of functional genetic polymorphism AGXT Pro11Leu in clinical outcome?
Main Author: | |
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Publication Date: | 2021 |
Other Authors: | , , , , , , |
Format: | Article |
Language: | eng |
Source: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Download full: | http://hdl.handle.net/10316/100782 https://doi.org/10.1016/j.pulmoe.2020.11.007 |
Summary: | 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. |
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Pharmacogenetics of advanced lung cancer: Predictive value of functional genetic polymorphism AGXT Pro11Leu in clinical outcome?Non-small cell lung cancerSingle nucleotide polymorphismPharmacogeneticsCohort studyAgedAntineoplastic AgentsCarboplatinCarcinoma, Non-Small-Cell LungCisplatinDisease ProgressionFemaleGenotypeHumansLung NeoplasmsMaleMiddle AgedNeoplasm StagingPharmacogeneticsPolymorphism, GeneticPredictive Value of TestsPrognosisProgression-Free SurvivalRetrospective StudiesSeverity of Illness IndexTransaminasesIntroduction 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.2021info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/100782http://hdl.handle.net/10316/100782https://doi.org/10.1016/j.pulmoe.2020.11.007eng25310437Catarata, Maria JoanaLourenço, MargaridaMartins, Maria FátimaFrade, JoãoPêgo, AliceCordeiro, Carlos RobaloMedeiros, RuiRibeiro, Ricardoinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2022-07-11T20:31:33Zoai:estudogeral.uc.pt:10316/100782Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:18:05.829469Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Pharmacogenetics of advanced lung cancer: Predictive value of functional genetic polymorphism AGXT Pro11Leu in clinical outcome? |
title |
Pharmacogenetics of advanced lung cancer: Predictive value of functional genetic polymorphism AGXT Pro11Leu in clinical outcome? |
spellingShingle |
Pharmacogenetics of advanced lung cancer: Predictive value of functional genetic polymorphism AGXT Pro11Leu in clinical outcome? Catarata, Maria Joana Non-small cell lung cancer Single nucleotide polymorphism Pharmacogenetics Cohort study Aged Antineoplastic Agents Carboplatin Carcinoma, Non-Small-Cell Lung Cisplatin Disease Progression Female Genotype Humans Lung Neoplasms Male Middle Aged Neoplasm Staging Pharmacogenetics Polymorphism, Genetic Predictive Value of Tests Prognosis Progression-Free Survival Retrospective Studies Severity of Illness Index Transaminases |
title_short |
Pharmacogenetics of advanced lung cancer: Predictive value of functional genetic polymorphism AGXT Pro11Leu in clinical outcome? |
title_full |
Pharmacogenetics of advanced lung cancer: Predictive value of functional genetic polymorphism AGXT Pro11Leu in clinical outcome? |
title_fullStr |
Pharmacogenetics of advanced lung cancer: Predictive value of functional genetic polymorphism AGXT Pro11Leu in clinical outcome? |
title_full_unstemmed |
Pharmacogenetics of advanced lung cancer: Predictive value of functional genetic polymorphism AGXT Pro11Leu in clinical outcome? |
title_sort |
Pharmacogenetics of advanced lung cancer: Predictive value of functional genetic polymorphism AGXT Pro11Leu in clinical outcome? |
author |
Catarata, Maria Joana |
author_facet |
Catarata, Maria Joana Lourenço, Margarida Martins, Maria Fátima Frade, João Pêgo, Alice Cordeiro, Carlos Robalo Medeiros, Rui Ribeiro, Ricardo |
author_role |
author |
author2 |
Lourenço, Margarida Martins, Maria Fátima Frade, João Pêgo, Alice Cordeiro, Carlos Robalo Medeiros, Rui Ribeiro, Ricardo |
author2_role |
author author author author author author author |
dc.contributor.author.fl_str_mv |
Catarata, Maria Joana Lourenço, Margarida Martins, Maria Fátima Frade, João Pêgo, Alice Cordeiro, Carlos Robalo Medeiros, Rui Ribeiro, Ricardo |
dc.subject.por.fl_str_mv |
Non-small cell lung cancer Single nucleotide polymorphism Pharmacogenetics Cohort study Aged Antineoplastic Agents Carboplatin Carcinoma, Non-Small-Cell Lung Cisplatin Disease Progression Female Genotype Humans Lung Neoplasms Male Middle Aged Neoplasm Staging Pharmacogenetics Polymorphism, Genetic Predictive Value of Tests Prognosis Progression-Free Survival Retrospective Studies Severity of Illness Index Transaminases |
topic |
Non-small cell lung cancer Single nucleotide polymorphism Pharmacogenetics Cohort study Aged Antineoplastic Agents Carboplatin Carcinoma, Non-Small-Cell Lung Cisplatin Disease Progression Female Genotype Humans Lung Neoplasms Male Middle Aged Neoplasm Staging Pharmacogenetics Polymorphism, Genetic Predictive Value of Tests Prognosis Progression-Free Survival Retrospective Studies Severity of Illness Index Transaminases |
description |
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. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/100782 http://hdl.handle.net/10316/100782 https://doi.org/10.1016/j.pulmoe.2020.11.007 |
url |
http://hdl.handle.net/10316/100782 https://doi.org/10.1016/j.pulmoe.2020.11.007 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
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25310437 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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