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The P38α rs3804451 Variant Predicts Chemotherapy Response and Survival of Patients with Non–Small Cell Lung Cancer Treated with Platinum-Based Chemotherapy()

The JNK and P38α pathways play an important role in the sensitivity and outcomes of chemotherapy. We hypothesize that functional single nucleotide polymorphisms (SNPs) of genes of these pathways modulate outcomes of patients with advanced non–small cell lung cancer (NSCLC) treated with first-line pl...

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Autores principales: Jia, Ming, Xu, Yuan, Zhu, Meiling, Wang, Mengyun, Sun, Menghong, Qian, Ji, Chang, Jianhua, Wei, Qingyi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109261/
https://www.ncbi.nlm.nih.gov/pubmed/27835790
http://dx.doi.org/10.1016/j.tranon.2016.09.006
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author Jia, Ming
Xu, Yuan
Zhu, Meiling
Wang, Mengyun
Sun, Menghong
Qian, Ji
Chang, Jianhua
Wei, Qingyi
author_facet Jia, Ming
Xu, Yuan
Zhu, Meiling
Wang, Mengyun
Sun, Menghong
Qian, Ji
Chang, Jianhua
Wei, Qingyi
author_sort Jia, Ming
collection PubMed
description The JNK and P38α pathways play an important role in the sensitivity and outcomes of chemotherapy. We hypothesize that functional single nucleotide polymorphisms (SNPs) of genes of these pathways modulate outcomes of patients with advanced non–small cell lung cancer (NSCLC) treated with first-line platinum-based chemotherapy (PBC). We selectively genotyped 11 independent, potentially functional SNPs of 9 genes in the JNK and P38α pathways first in a discovery group of 355 patients with advanced NSCLC treated with PBC, and we evaluated their associations with progression-free survival (PFS) and overall survival (OS) by Cox proportional hazards regression analysis. Then, resultant significant SNPs were further validated in a replication group of 355 patients. In both discovery and validation groups as well as their combined analysis, the MAPK14 rs3804451GA/AA genotypes showed a strong association with a reduced PFS (adjusted hazards ratio [HR] = 1.39; 95% confidence interval [CI] = 1.16–1.66; P = .0003) and OS (adjusted HR = 1.41; 95% CI = 1.11-1.80; P = .005) compared with the wild-type GG genotype. In contrast, patients with or without the MAPK14 rs3804451A allele had no significant difference in OS in response to tyrosine-kinase inhibitor treatment (adjusted HR = 0.86; 95% CI = 0.56-1.33; P = .505). The present study provides evidence that the MAPK14 rs3804451 G>A variant may modulate survival outcomes in patients with advanced NSCLC treated with PBC. Larger studies of additional patient populations are needed to validate our findings.
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spelling pubmed-51092612016-11-21 The P38α rs3804451 Variant Predicts Chemotherapy Response and Survival of Patients with Non–Small Cell Lung Cancer Treated with Platinum-Based Chemotherapy() Jia, Ming Xu, Yuan Zhu, Meiling Wang, Mengyun Sun, Menghong Qian, Ji Chang, Jianhua Wei, Qingyi Transl Oncol Original article The JNK and P38α pathways play an important role in the sensitivity and outcomes of chemotherapy. We hypothesize that functional single nucleotide polymorphisms (SNPs) of genes of these pathways modulate outcomes of patients with advanced non–small cell lung cancer (NSCLC) treated with first-line platinum-based chemotherapy (PBC). We selectively genotyped 11 independent, potentially functional SNPs of 9 genes in the JNK and P38α pathways first in a discovery group of 355 patients with advanced NSCLC treated with PBC, and we evaluated their associations with progression-free survival (PFS) and overall survival (OS) by Cox proportional hazards regression analysis. Then, resultant significant SNPs were further validated in a replication group of 355 patients. In both discovery and validation groups as well as their combined analysis, the MAPK14 rs3804451GA/AA genotypes showed a strong association with a reduced PFS (adjusted hazards ratio [HR] = 1.39; 95% confidence interval [CI] = 1.16–1.66; P = .0003) and OS (adjusted HR = 1.41; 95% CI = 1.11-1.80; P = .005) compared with the wild-type GG genotype. In contrast, patients with or without the MAPK14 rs3804451A allele had no significant difference in OS in response to tyrosine-kinase inhibitor treatment (adjusted HR = 0.86; 95% CI = 0.56-1.33; P = .505). The present study provides evidence that the MAPK14 rs3804451 G>A variant may modulate survival outcomes in patients with advanced NSCLC treated with PBC. Larger studies of additional patient populations are needed to validate our findings. Neoplasia Press 2016-11-08 /pmc/articles/PMC5109261/ /pubmed/27835790 http://dx.doi.org/10.1016/j.tranon.2016.09.006 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original article
Jia, Ming
Xu, Yuan
Zhu, Meiling
Wang, Mengyun
Sun, Menghong
Qian, Ji
Chang, Jianhua
Wei, Qingyi
The P38α rs3804451 Variant Predicts Chemotherapy Response and Survival of Patients with Non–Small Cell Lung Cancer Treated with Platinum-Based Chemotherapy()
title The P38α rs3804451 Variant Predicts Chemotherapy Response and Survival of Patients with Non–Small Cell Lung Cancer Treated with Platinum-Based Chemotherapy()
title_full The P38α rs3804451 Variant Predicts Chemotherapy Response and Survival of Patients with Non–Small Cell Lung Cancer Treated with Platinum-Based Chemotherapy()
title_fullStr The P38α rs3804451 Variant Predicts Chemotherapy Response and Survival of Patients with Non–Small Cell Lung Cancer Treated with Platinum-Based Chemotherapy()
title_full_unstemmed The P38α rs3804451 Variant Predicts Chemotherapy Response and Survival of Patients with Non–Small Cell Lung Cancer Treated with Platinum-Based Chemotherapy()
title_short The P38α rs3804451 Variant Predicts Chemotherapy Response and Survival of Patients with Non–Small Cell Lung Cancer Treated with Platinum-Based Chemotherapy()
title_sort p38α rs3804451 variant predicts chemotherapy response and survival of patients with non–small cell lung cancer treated with platinum-based chemotherapy()
topic Original article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109261/
https://www.ncbi.nlm.nih.gov/pubmed/27835790
http://dx.doi.org/10.1016/j.tranon.2016.09.006
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