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Genetic variants of GADD45A, GADD45B and MAPK14 predict platinum-based chemotherapy-induced toxicities in Chinese patients with non-small cell lung cancer.

dc.contributor.author Jia, Ming
dc.contributor.author Zhu, Meiling
dc.contributor.author Wang, Mengyun
dc.contributor.author Sun, Menghong
dc.contributor.author Qian, Ji
dc.contributor.author Ding, Fei
dc.contributor.author Chang, Jianhua
dc.contributor.author Wei, Qingyi
dc.date.accessioned 2019-02-01T15:22:44Z
dc.date.available 2019-02-01T15:22:44Z
dc.date.issued 2016-05
dc.identifier 8052
dc.identifier.issn 1949-2553
dc.identifier.issn 1949-2553
dc.identifier.uri https://hdl.handle.net/10161/18005
dc.description.abstract The JNK and P38α pathways play a crucial role in tissue homeostasis, apoptosis and autophagy under genotoxic stresses, but it is unclear whether single nucleotide polymorphisms (SNPs) of genes in these pathways play a role in platinum-based chemotherapy-induced toxicities in patients with advanced non-small cell lung cancer (NSCLC). We genotyped 11 selected, independent, potentially functional SNPs of nine genes in the JNK and P38α pathways in 689 patients with advanced NSCLC treated with platinum-combination chemotherapy regimens. Associations between these SNPs and chemotherapy toxicities were tested in a discovery group of 345 patients and then validated in a replication group of 344 patients. In both discovery and validation groups as well as their pooled analysis, carriers of GADD45B rs2024144T variant allele had a significantly higher risk for severe hematologic toxicity and carriers of MAPK14 rs3804451A variant allele had a significantly higher risk for both overall toxicity and gastrointestinal toxicity. In addition, carriers of GADD45A rs581000C had a lower risk of anemia, while carriers of GADD45B rs2024144T had a significantly higher risk for leukocytopenia or agranulocytosis. The present study provides evidence that genetic variants in genes involved in the JNK and P38α pathways may predict platinum-based chemotherapy toxicity outcomes in patients with advanced NSCLC. Larger studies of other patient populations are needed to validate our findings.
dc.language eng
dc.publisher Impact Journals, LLC
dc.relation.ispartof Oncotarget
dc.relation.isversionof 10.18632/oncotarget.8052
dc.subject Humans
dc.subject Carcinoma, Non-Small-Cell Lung
dc.subject Lung Neoplasms
dc.subject Genetic Predisposition to Disease
dc.subject Cisplatin
dc.subject Carboplatin
dc.subject Mitogen-Activated Protein Kinase 14
dc.subject Cell Cycle Proteins
dc.subject Nuclear Proteins
dc.subject Antineoplastic Combined Chemotherapy Protocols
dc.subject Antigens, Differentiation
dc.subject Genotype
dc.subject Polymorphism, Single Nucleotide
dc.subject Adult
dc.subject Aged
dc.subject Aged, 80 and over
dc.subject Middle Aged
dc.subject Asian Continental Ancestry Group
dc.subject Female
dc.subject Male
dc.subject Young Adult
dc.title Genetic variants of GADD45A, GADD45B and MAPK14 predict platinum-based chemotherapy-induced toxicities in Chinese patients with non-small cell lung cancer.
dc.type Journal article
duke.contributor.id Wei, Qingyi|0632334
dc.date.updated 2019-02-01T15:22:40Z
pubs.begin-page 25291
pubs.end-page 25303
pubs.issue 18
pubs.organisational-group School of Medicine
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Population Health Sciences
pubs.organisational-group Basic Science Departments
pubs.organisational-group Medicine, Medical Oncology
pubs.organisational-group Medicine
pubs.organisational-group Clinical Science Departments
pubs.publication-status Published
pubs.volume 7
duke.contributor.orcid Wei, Qingyi|0000-0002-3845-9445


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