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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.
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.
Type
Journal articleSubject
HumansCarcinoma, Non-Small-Cell Lung
Lung Neoplasms
Genetic Predisposition to Disease
Cisplatin
Carboplatin
Mitogen-Activated Protein Kinase 14
Cell Cycle Proteins
Nuclear Proteins
Antineoplastic Combined Chemotherapy Protocols
Antigens, Differentiation
Genotype
Polymorphism, Single Nucleotide
Adult
Aged
Aged, 80 and over
Middle Aged
Asian Continental Ancestry Group
Female
Male
Young Adult
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https://hdl.handle.net/10161/18005Published Version (Please cite this version)
10.18632/oncotarget.8052Publication Info
Jia, Ming; Zhu, Meiling; Wang, Mengyun; Sun, Menghong; Qian, Ji; Ding, Fei; ... Wei,
Qingyi (2016). Genetic variants of GADD45A, GADD45B and MAPK14 predict platinum-based chemotherapy-induced
toxicities in Chinese patients with non-small cell lung cancer. Oncotarget, 7(18). pp. 25291-25303. 10.18632/oncotarget.8052. Retrieved from https://hdl.handle.net/10161/18005.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Qingyi Wei
Professor in Population Health Sciences
Qingyi Wei, MD, PhD, Professor in the Department of Medicine, is Associate Director
for Cancer Control and Population Sciences, Co-leader of CCPS and Co-leader of Epidemiology
and Population Genomics (Focus Area 1). He is a professor of Medicine and an internationally
recognized epidemiologist focused on the molecular and genetic epidemiology of head
and neck cancers, lung cancer, and melanoma. His research focuses on biomarkers and
genetic determinants for the DNA repair deficient phenotype and

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